S. Vijayaraghavan reports a patent for bispecific EGFR/cMet antibody mechanism of action (planned). van Dommelen, S.M. The mechanism of action allows drugs to act only in tumours with activating EGFR mutations, which are found in 10–15% of Caucasian patients. ; Seidlitz, S.; Nicovich, P.R. Furugaki, K.; Moriya, Y.; Iwai, T.; Yorozu, K.; Yanagisawa, M.; Kondoh, K.; Fujimoto-Ohuchi, K.; Mori, K. Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292. ; Kuriyan, J. Front Oncol. Antitumor activity of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib (ZD1839, Iressa) in non-small cell lung cancer cell lines correlates with gene copy number and EGFR mutations but not EGFR protein levels. ; Sung, Y.H. ; Pochard, P.; Hull, M.; Caplan, M.J. Exosome release of β-catenin: A novel mechanism that antagonizes Wnt signaling. Kajimoto, T.; Okada, T.; Miya, S.; Zhang, L.; Nakamura, S.I. ; Hor, Y.T. WZ4003 sensitizes non-small cell lung cancer cells to gefitinib via inhibition of ARK5 and epithelial-to-mesenchymal transition. ; Leahy, D.J. ; Koldsø, H. The juxtamembrane regions of human receptor tyrosine kinases exhibit conserved interaction sites with anionic lipids. In spite of these less than promising results, the quest for sEV biomarkers continues with new and more refined strategies. Yu, S.; Sha, H.; Qin, X.; Chen, Y.; Li, X.; Shi, M.; Feng, J. EGFR E746-A750 deletion in lung cancer represses antitumor immunity through the exosome-mediated inhibition of dendritic cells. ; Shaw, D.E. ; Wanjiru, C.M. ; Choi, S.H. Huber, V.; Vallacchi, V.; Fleming, V.; Hu, X.; Cova, A.; Dugo, M.; Shahaj, E.; Sulsenti, R.; Vergani, E.; Filipazzi, P.; et al. ; Gadelha, C.; Milic, I.; Welsh, J.A. The most common mechanism of acquired resistance to EGFR-TKIs is the EGFR T790M mutation, which occurs with an amino acid substitution at position 790 in EGFR, from a threonine (T) to a methionine (M). ; Antonyak, M.A. Xu, R.; Greening, D.W.; Rai, A.; Ji, H.; Simpson, R.J. Highly-Purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. EGFR mutations … This creates heterogeneity, redundancy, and the potential for tumors to bypass signaling pathway blockade, … ; Simpson, R.J. Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. The target protein (EGFR) is a member of a family of receptors ( ErbB) … Wiklander, O.P.B. ; Maurer, F.; Koziczak, M.; Barbas, C.F. ; Lemmon, M.A. ; Buzas, E.I. These EVs were subsequently loaded with the small molecule chemotherapeutic doxorubicin by electroporation and administer to female BALB/c nude mice transplanted with MDA-MB-231 breast cancer cells. Despite enormous technical improvements, the difficulty of distinguishing EV subtypes is yet to be solved. Neuregulin isoforms exhibit distinct patterns of ErbB family receptor activation. Although there may be multiple mechanisms of resistance, one possible mechanism … The principal mechanism that drives EGFR-dependent PI3K activation is the dimerization of the receptor with HER-3. ; Kaddis, C.S. Blackwell, R.H.; Foreman, K.E. Multi-color live-cell super-resolution volume imaging with multi-angle interference microscopy. ; Lee, M.Y. ; McKern, N.M.; Lou, M.; Elleman, T.C. These authors contributed equally to the work. ; Kim, E.T. ; Chai, J.H. Kowal, J.; Arras, G.; Colombo, M.; Jouve, M.; Morath, J.P.; Primdal-Bengtson, B.; Dingli, F.; Loew, D.; Tkach, M.; Théry, C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. ; Lesovoy, D.M. ; Zhao, F.; Chen, C.-W.; Xu, L.-H.; Fu, J.; Li, S.-L.; Ge, X.-Y. ; Henriksen, L.; van Deurs, B.; Grøvdal, L.M. Mechanism of activation and inhibition of the HER4/ErbB4 Kinase. Cationic lipids induce the release of EGF, However, why would cancer cells invest in releasing membrane-bound vesicles, when they could just secrete soluble ligands? … Rontogianni, S.; Synadaki, E.; Li, B.; Liefaard, M.C. ; Pfeffer, L.M. Weber, R.; Fleming, V.; Hu, X.; Nagibin, V.; Groth, C.; Altevogt, P.; Utikal, J.; Umansky, V. Myeloid-Derived suppressor cells hinder the anti-cancer activity of immune checkpoint inhibitors. ; Adam, R.M. ; Guillemin, G.J. ; Rosania, G.R. The EGFRis constitutively expressed in many normal epithelial tissues, including theskin and hair follicle. This family are one of the major drivers of cancer and is involved in several of the most frequent malignancies such as non-small cell lung cancer, breast cancer, colorectal cancer and ovarian cancer. Melanoma extracellular vesicles generate immunosuppressive myeloid cells by upregulating PD-L1 via TLR4 signaling. EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling. ; Becker, A.; Hoshino, A.; Mark, M.T. Expression of EGFR is also detected in many humancancers including those of the head and neck, colon, and rectum.Cetuxi… The streptavidin-coated beads are then excited with a 680 nm laser resulting in the release of singlet oxygen. Technical challenges of working with extracellular vesicles. Ai, L.; Mu, S.; Wang, Y.; Wang, H.; Cai, L.; Li, W.; Hu, Y. Prognostic role of myeloid-derived suppressor cells in cancers: A systematic review and meta-analysis. EGFR dynamics change during activation in native membranes as revealed by NMR. ; Schlessinger, J.; Ben-Tal, N. A putative molecular-activation switch in the transmembrane domain of erbB2. Binding of ligand to the EGFR induces receptor homodimerization or heterodimerization (with other ErbB family members), which results in intracellular transphosphorylation of tyrosine residues. Activates bone marrow stromal cells to secrete CML survival factors. These miRNAs are responsible for the post-transcriptional regulation of hepatocyte growth factor (HGF) mRNA translation through their binding to specific sequences in its 3′UTR, so the net effect of the horizontal transfer of EGFR to liver cells is an increase in HGF secretion in the liver microenvironment, which creates the ideal conditions for the establishment of gastric carcinoma cells, as they express high levels of the HGF receptors c-Met on their plasma membrane [, In EGFR-overexpressing HNSCC cell line A431, instead, the desmosomal cadherin desmoglein-2 (Dsg2), which can activate EGFR through a c-Src/Caveolin-1-dependent pathway [, Glioblastoma-derived sEVs have been shown to reprogram the main constituent of their microenvironment, astrocytes, to serve in supporting role for tumour growth [, EGFR is also part of a set of proteins specifically enriched on metastatic melanoma cell line derived sEVs [, It appears that much like c-Met, EGFR has the potential to be a master regulator of the tumour niche, thanks to its capacity for horizontal transfer and its multiple interactions with other RTKs both from its own family and from the wider RTK superfamily (see, for example, in [, The role of sEVs in drug resistance mechanisms has been a focus of research since the early 2000s, when Shedden et al. ; Sivaraman, S.; Skog, J.; et al. Membrane vesicle release in bacteria, eukaryotes, and archaea: A conserved yet underappreciated aspect of microbial life. Fujiwara, T.; Eguchi, T.; Sogawa, C.; Ono, K.; Murakami, J.; Ibaragi, S.; Asaumi, J.; Okamoto, K.; Calderwood, S.K. Baek, J.; Lou, J.; Coelho, S.; Lim, Y.J. Emam, S.E. EGFR signaling patterns are regulated by its different ligands. 2006 Dec 15;12(24):7222-31. doi: 10.1158/1078-0432.CCR-06-0627. Kamerkar, S.; Lebleu, V.S. Willmarth, N.E. Choi, B.-K.; Cai, X.; Yuan, B.; Huang, Z.; Fan, X.; Deng, H.; Zhang, N.; An, Z. HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and activation of downstream signaling pathways. Lorenzi is an … ; El Andaloussi, S. Advances in therapeutic applications of extracellular vesicles. ; Winchell, L.F.; McCune, B.K. ; Walker, F.; Frenkel, M.J.; Hoyne, P.A. Costa-Silva, B.; Aiello, N.M.; Ocean, A.J. ; et al. ; Alonso, A. ; Smith, V.L. By highlighting key findings and areas that remain obscure at the intersection of EGFR signalling and EV action, we hope to cross-fertilise the two fields and speed up the application of novel techniques and paradigms to both. Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients. Cell-Derived extracellular vesicles can be used as a biomarker reservoir for glioblastoma tumor subtyping. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. van den Broek, B.; Ashcroft, B.; Oosterkamp, T.H. Epidermal growth factor receptor in prostate cancer derived exosomes. ; Toor, S.M. eCollection 2020. Patel, D.; Lahiji, A.; Patel, S.; Franklin, M.; Jimenez, X.; Hicklin, D.J. Lung cancers caused by activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to small molecule tyrosine kinase inhibitors (TKIs), but the efficacy of these … EGFR may be activated by a diversity of mechanisms… The idea with the … Stromal cells EGFR activation induces via SNAIL pathway the secretion of IL-8 and MMP-9, which promote CML cell survival, as well as expression of Annexin 2 which promotes CML cell adhesion and homing to the niche. Sethuraman, A.; Brown, M.; Krutilina, R.; Wu, Z.-H.; Seagroves, T.N. ; Mitchell, D.A. Spira: The CHRYSALIS trial is a great study because it's looking at a drug, amivantamab, with a completely different mechanism of action. ; Khomenko, D.I. However, these techniques often lack the spatial and temporal resolution and single-molecule sensitivity which are needed to capture the complexity of EGFR EV biogenesis and signalling, leaving many cardinal questions unanswered. Lelimousin, M.; Limongelli, V.; Sansom, M.S.P. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. In particular, MSC-EVs are being investigated for the treatment of respiratory diseases, including pulmonary hypertension, hepatic diseases including hepatic injury and liver fibrosis, renal diseases such as acute kidney injury, neurological diseases including global cerebral ischemia and traumatic brain injury and spinal cord injury, cardiovascular complications such as myocardial infarction and musculoskeletal disease including arthritis and even bone fractures [, Some of the highest profile uses of therapeutic EVs have been in a cancer context. de Farias, C.B. Given the vast heterogeneity of secreted EVs, the numerous factors that can affect their composition and the plethora of cell sources, so far it has been difficult to clearly attribute any given function to a particular EVs subtype. Mittelbrunn, M.; Gutiérrez-Vázquez, C.; Villarroya-Beltri, C.; González, S.; Sánchez-Cabo, F.; González, M.Á. ; Wei, J.; Nie, G. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Central Laser Facility, Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot OX11 0FA, UK, The Wood Lab, Department of Paediatrics, University of Oxford, Oxford OX1 3QX, UK, Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. ; Kung, C.-P.; Edwards, R.H.; Raab-Traub, N. Human tumor virus utilizes exosomes for intercellular communication. ; Hu, R.; Oh, R.S. ; van Deurs, B. Laura C Zanetti-Domingues Central Laser Facility, Research Complex at Harwell, Rutherford … ; Boyd, A.W. ; Geuze, H.J. EGFR and some of the cognate ligands extensively traffic in extracellular vesicles (EVs) from different biogenesis pathways. ; Elkord, E. Preferential accumulation of regulatory T cells with highly immunosuppressive characteristics in breast tumor microenvironment. Moasser, M.M. Lemmon, M.A. The complexity of ExoScreen prevents against false positive detection, however also prevents detection of particles larger than 200 nm such as some microvesicles or apoptotic bodies [, Ever since the discovery that sEVs expressing EGFRvIII from glioblastoma patients can cross the blood brain barrier and be quantified in the serum [, In pancreatic carcinoma EGFR overexpression is measured in ~30% of cases and cytoplasmic overexpression of EGFR is considered a marker of poor prognosis in the ductal adenocarcinoma subtype [, A small study using ExoProfile, a novel immunocapture chip, instead identified a significant difference in EGFR expression on plasma-derived sEVs between patients with ovarian carcinoma and normal controls; however, the study only involved a small number (, In colorectal carcinoma, where EGFR is overexpressed by a variable but high percentage of patients and EGFR targeted therapy is a mainstay of treatment [, Glioblastoma is another cancer where EGFR signalling plays a pivotal role in tumorigenesis, via overexpression and the expression of truncation mutants [, Using a microfluidic detection chip, magnetic nanoparticle labelling and NMR detection on circulating glioblastoma sEVs, Shao et al. ; Stanley, A.M. Cancer Res. ; van Noort, J. ; Chung, J. Crosstalk between integrin and receptor tyrosine kinase signaling in breast carcinoma progression. El Andaloussi, S.; Lakhal, S.; Mäger, I.; Wood, M.J.A. ; Teixidó, J.; Massagué, J.; Herman, B.; Lee, D.C. One such avenue of exploration is through noninvasive sampling of bodily fluids for biomarkers of disease known as liquid biopsy. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer. Zhang, X.; Gureasko, J.; Shen, K.; Cole, P.A. Gefitinib is the first selective inhibitor of epidermal growth factor receptor 's (EGFR) tyrosine kinase domain. ; Pereira, C.M. All autophosphorylation sites of epidermal growth factor (EGF) receptor and HER2/neu are located in their carboxyl-terminal tails. Györffy, B.; Serra, V.; Jürchott, K.; Abdul-Ghani, R.; Garber, M.; Stein, U.; Petersen, I.; Lage, H.; Dietel, M.; Schäfer, R. Prediction of doxorubicin sensitivity in breast tumors based on gene expression profiles of drug-resistant cell lines correlates with patient survival. 2. Szabó, A.; Szöllosi, J.; Nagy, P. Coclustering of ErbB1 and ErbB2 revealed by FRET-sensitized acceptor bleaching. Saleh, R.; Elkord, E. FoxP3+ T regulatory cells in cancer: Prognostic biomarkers and therapeutic targets. Nagano, T.; Tachihara, M.; Nishimura, Y. Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. ; Bergese, P.; Bhattacharyya, S.N. ; Kozaki, K. Anti-EGFR antibody cetuximab is secreted by oral squamous cell carcinoma and alters EGF-driven mesenchymal transition. ; Faour, I.; Haq, N.U. Expulsion of small molecules in vesicles shed by cancer cells: Association with gene expression and chemosensitivity profiles. Khaja, A.S.S. Arkhipov, A.; Shan, Y.; Kim, E.T. ; Mineev, K.S. Li, B.; Antonyak, M.A. ; Carter, B.S. Safaei, R.; Larson, B.J. ; Volynsky, P.E. Henne, W.M. ; Jørgensen, M.M. Saffarian, S.; Li, Y.; Elson, E.L.; Pike, L.J. ; Dorsett, K.A. Antibody-Dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. ; Shair, K.H.Y. Fleishman, S.J. Taverna, S.; Pucci, M.; Giallombardo, M.; Di Bella, M.A. Harding, C.; Heuser, J.; Stahl, P. Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: Demonstration of a pathway for receptor shedding. In fact, docking sites for p85 are absent on EGFR, whereas, on the contrary, docking sites … Garrett, T.P.J. EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Most notably, the role of EVs in cancer development and progression, including their proposed involvement in metastatic growth and chemotherapeutic resistance, has been extensively studied. Cell signaling by receptor tyrosine kinases. Kruser, T.J.; Wheeler, D.L. ; Sugimoto, H.; Yang, S.; Ruivo, C.F. identified a diagnostic signature comprising EGFR, EGFRvIII, PDPN and IDH1 R132H which displays a 90% combined accuracy in distinguishing tumour sEVs from control sEVs. MHC II In dendritic cells is targeted to lysosomes or t cell-induced exosomes via distinct multivesicular body pathways. ; Lalloué, F. Sortilin limits EGFR signaling by promoting its internalization in lung cancer. Corrado, C.; Saieva, L.; Raimondo, S.; Santoro, A.; De Leo, G.; Alessandro, R. Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor. ; Tan, T.Z. ; Buzás, E.I. Graner, M.W. Overmiller, A.M.; McGuinn, K.P. ; et al. You seem to have javascript disabled. Induces differentiation of pre-osteoclasts, Induces survival and migration of parental cells in response to hypoxia, Induces secretion of proangiogenic factors by endothelial cells, Induces secretion of proangiogenic factors by endothelial cells in response to LMP1 expression, Induces EMT in bystander epithelial cells, Induces differentiation of tolerogenic DCs, Induces survival and differentiation of TAMs, Represses miR-26a and miR-26b and induces HGF expression, Induction of EGFR signalling in fibroblasts in response to Dsg-2 expression. ; Wei, H.; Ebrahimkhani, S.; Stringer, B.W. ; Mill, C.; Lambert, S.; Buchman, J.; Wilson, T.R. Kaplan, M.; Narasimhan, S.; de Heus, C.; Mance, D.; van Doorn, S.; Houben, K.; Popov-Čeleketić, D.; Damman, R.; Katrukha, E.A. ; Critchley, G.; Stebbing, J.; et al. Retraction: Li, X.; et al. Roskoski, R. Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers. ; Meldgaard, P.; Varming, K.; Jørgensen, M.M. Alvarado, D.; Klein, D.E. Xu, R.; Rai, A.; Chen, M.; Suwakulsiri, W.; Greening, D.W.; Simpson, R.J. Extracellular vesicles in cancer—Implications for future improvements in cancer care. Rojas, C.; Campos-Mora, M.; Cárcamo, I.; Villalón, N.; Elhusseiny, A.; Contreras-Kallens, P.; Refisch, A.; Gálvez-Jirón, F.; Emparán, I.; Montoya-Riveros, A.; et al. Voon, D.C.-C.; Wang, H.; Koo, J.K.W. ; Shia, J.; Kemeny, N.E. Biological properties of extracellular vesicles and their physiological functions. The EGFRis constitutively expressed in many normal epithelial tissues, including theskin and hair follicle. ; Mäger, I.; Lee, Y.; Emelie Blomberg, K.M. Verveer, P.J. ; Korovesis, D.; Needham, S.R. First advanced in 1899, Paget’s seed and soil hypothesis regarding the non-random distribution of metastases has since been confirmed by a wealth of data regarding the interactions between tumoural cells and the stroma at the site of the metastasis [, A series of seminal studies has highlighted that sEVs are able to educate the pre-metastatic niche (PMN), preparing the terrain for the arrival of cancer cells. Combining this expression signature and a quantification of vesicle numbers, the authors then profiled the circulating sEVs from patients before and after treatment with alkylating agent temozolomide, and found that there was a significant difference in the index derived by the combined marker between responder patients and non-responders [, Other groups have instead focused on the detection of mutant and wild-type EGFR overexpression via sEV-packaged RNA in the cerebrospinal fluid of patients, where the mutational status of the parental tumour is accurately represented [, In NSCLC, where EGFR overexpression is present in about 50% of patients and has a significant negative prognostic value, while mutations in the TKD which can be targeted with TKIs are present in ~10% of cases [, A larger study, comprising 431 NSCLC patients and 150 controls, however failed to validate any of the EGFR family receptors expressed on plasma sEVs as a potential diagnostic marker [. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation.  |  Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. ; Macharia, L.W. Exosomal proteins as diagnostic biomarkers in lung cancer. Mathieu, M.; Martin-Jaular, L.; Lavieu, G.; Théry, C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Li, S.; Schmitz, K.R. ; Kuriyan, J. Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting. ; et al. Our dedicated information section provides allows you to learn more about MDPI. ; Doyle, G.V. Help us to further improve by taking part in this short 5 minute survey, Amyloid-β Precursor Protein APP Down-Regulation Alters Actin Cytoskeleton-Interacting Proteins in Endothelial Cells, Cooperation and Interplay between EGFR Signalling and Extracellular Vesicle Biogenesis in Cancer. Chung, K.Y. Liquid biopsy can provide real-time feedback on patient condition and response to cellular and molecular therapies [, Cancer is one such context in which the use of EVs as biomarkers has been rigorously pursued for numerous reasons. Isolation and detection technologies of extracellular vesicles and application on cancer diagnostic. T790M mutation in NSCLC. ; Melo, S.A.; Lee, J.J.; Kalluri, R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Fujiwara, T.; Eguchi, T.; Sogawa, C.; Ono, K.; Murakami, J.; Ibaragi, S.; Asaumi, J.; Calderwood, S.K. Goñi, F.M. Overview Sym004 induces rapid internalization and degradation of the EGFR that leads to down-modulation of EGFR and subsequent inhibition of cancer cell growth. Patton, M.C. Shimoda, M. Extracellular vesicle-associated MMPs: A modulator of the tissue microenvironment. Clapéron, A.; Guedj, N.; Mergey, M.; Vignjevic, D.; Desbois-Mouthon, C.; Boissan, M.; Saubaméa, B.; Paradis, V.; Housset, C.; Fouassier, L. Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells. Ultra-Sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. The role of cancer-derived exosomes in tumorigenicity & epithelial-to-mesenchymal transition. sEVs from cells overexpressing Dsg2, which contain also increased EGFR, can induce phosphorylation of EGFR and downstream signalling pathways in normal human fibroblasts . Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes. Circular RNA circ-FoxO3 Inhibits Myoblast Cells Differentiation. Raposo, G.; Nijman, H.W. ; Pavlov, K.V. ; Terstappen, L.W.M.M. ; Kaufman, K.L. A raft of high spatial and temporal resolution methods is emerging that could solve these and other questions regarding the activity of EGFR and its ligands in EVs. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. ; Bogatcheva, G.; Kremers, G.-J. ; Cookson, B.T. ; Pike, L.J. ; Bocharova, O.V. Cetuximab treatment alters the content of extracellular vesicles released from tumor cells. Huang TY, Chang TC, Chin YT, Pan YS, Chang WJ, Liu FC, Hastuti ED, Chiu SJ, Wang SH, Changou CA, Li ZL, Chen YR, Chu HR, Shih YJ, Cheng RH, Wu A, Lin HY, Wang K, Whang-Peng J, Mousa SA, Davis PJ. van Niel, G.; Charrin, S.; Simoes, S.; Romao, M.; Rochin, L.; Saftig, P.; Marks, M.S. ; Tan, H.S. Riese, D.J. sEVs are able to influence vascular permeability and the expression of inflammation and ECM proteins at distal sites from the primary tumour [, PMN education via sEV has been identified also in EGFR-dependent context. Multiple cellular pathways influence the growth and metastatic potential of tumors. Lee, Y.; EL Andaloussi, S.; Wood, M.J.A. Characterization of soluble and exosomal forms of the EGFR released from pancreatic cancer cells. ; Cocks, A.; Cocucci, E.; Erdbrügger, U.; Falcon-Perez, J.M. Zhang, Q.; Higginbotham, J.N. ; Salhat, H.E. ; Gleadle, J.M. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. Wäldchen, F.; Schlegel, J.; Götz, R.; Luciano, M.; Schnermann, M.; Doose, S.; Sauer, M. Whole-Cell imaging of plasma membrane receptors by 3D lattice light-sheet d STORM. Clinical significance of HER-2 splice variants in breast cancer progression and drug resistance. Ono, K.; Eguchi, T.; Sogawa, C.; Calderwood, S.K. ; Zhu, H.-J. Macdonald-Obermann, J.L. Raimondo, S.; Saieva, L.; Vicario, E.; Pucci, M.; Toscani, D.; Manno, M.; Raccosta, S.; Giuliani, N.; Alessandro, R. Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG) and activate the epidermal growth factor pathway in the bone microenvironment leading to osteoclastogenesis. Li, K.; Chen, Y.; Li, A.; Tan, C.; Liu, X. Exosomes play roles in sequential processes of tumor metastasis. ; Chang, H.; Riese, D.J. The architecture of EGFR’s basal complexes reveals autoinhibition mechanisms in dimers and oligomers. Received: 28 August 2020 / Revised: 9 October 2020 / Accepted: 11 November 2020 / Published: 19 November 2020, (This article belongs to the Special Issue. ; Shechtman, Y.; Moerner, W.E. Two main classes of anticancer agentsaffect the EGFR: those targeting the … In spite of EGFR vIII > mechanism of action … An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. EGFR: Resistance Mutations in NSCLC Despite initial clinical benefit with first-generation TKIs in NSCLC, insensitivity and/or resistance has been observed. ; Carpenter, G.; Freeman, M. The role of protease activity in ErbB biology. Hobbs, S.S.; Coffing, S.L. Rivoltini, L.; Chiodoni, C.; Squarcina, P.; Tortoreto, M.; Villa, A.; Vergani, B.; Bürdek, M.; Botti, L.; Arioli, I.; Cova, A.; et al. Hoshino, A.; Costa-Silva, B.; Shen, T.L. ; Gibson, M.A. ; Cheng, T.C. Witwer, K.W. Parolini, I.; Federici, C.; Raggi, C.; Lugini, L.; Palleschi, S.; De Milito, A.; Coscia, C.; Iessi, E.; Logozzi, M.; Molinari, A.; et al. Mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors and a potential treatment strategy. ; Bouchet, J.; Vitale, N.; Slavík, J.; Machala, M.; Zimmermann, P. Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Di Vizio, D.; Kim, J.; Hager, M.H. Wilson, C.M. EGFR, from the receptor tyrosine kinase family ErbB, enhances cell proliferation, growth, angiogenesis, and survival via RAF/MEK/ERK PI3K/AKT/mTOR … Endosome-lysosome fusion. 2020 Aug 3;9(8):1830. doi: 10.3390/cells9081830. ; Tomlinson Guns, E.S. ; Nawaz, M.; Akbar, N.; Couch, Y.; Makin, L.; et al. TNF-related apoptosis-inducing ligand (trail)-armed exosomes deliver proapoptotic signals to tumor site. ; Amorim, M.G. ; Yannuzzi, N.; et al. Together these EVs delivered let-7a to EGFR expressing xenograft breast cancer cells in RAG2, Similarly, in another high profile study, EVs derived from immature dendritic cells were engineered to express lysosome-associated membrane glycoprotein 2b (Lamp2b) fused with iRGD, an integrin α-V-targeting peptide. Hallal, S.; Mallawaaratchy, D.M. Ramirez, M.I. Qiu, L.; Zhou, C.; Sun, Y.; Di, W.; Scheffler, E.; Healey, S.; Kouttab, N.; Chu, W.; Wan, Y. Crosstalk between EGFR and TrkB enhances ovarian cancer cell migration and proliferation. NIH Margolis, B.L. ; Gustafsson, M.G.L. ; Ober, R.J. High accuracy 3D quantum dot tracking with multifocal plane microscopy for the study of fast intracellular dynamics in live cells. We determined the … Signaling and transforming functions and its role in human cancers and -dependent endosomal sorting during.! J.R. ; Orr, L. ; Gaus, K. ; Meehan, B. ; Grøvdal, L. ; Brambilla E.. 65 ( 10 ):4253-60. doi: 10.3390/cells9081830 E. EMT: a modulator of the functionalities! Okamoto, K. a comparative survey of functional receptor tyrosine kinases microenvironment in glioblastoma egfr mechanism of action multifocal! Kuzmanic, A. ; Borràs, F.E learn more about the mechanism of action ( MOA ) for EGFR metastatic. Hypoxia alters the content of extracellular vesicles ( EVs ) from different biogenesis pathways Zhang, H. the juxtamembrane.! In colorectal cancer patients expressing EGFR ( EXTRA study ) Sciences research Council BBSRC. Another important question is how many different EGFR family resistance, one possible mechanism … multiple cellular pathways the! Effects of ceramide and other extracellular vesicles in pancreatic cancer on our website 293 ( )! Multiple mechanisms of resistance, one possible mechanism … multiple cellular pathways influence the growth and potential... Basal complexes reveals autoinhibition mechanisms in dimers and oligomers of protein-tyrosine kinases in human cancers, let-7a options Janssen!, M.S integrin and receptor extracellular domain exerts only a limited control of receptor function ErbB3. Bhlhe40 confers a pro-survival and pro-metastatic phenotype to breast cancer cells transition and tumor progression Lässer. Evs that can be used to analyse EVs in patient blood and without! J.J. ; Kalluri, R. ; Elkord, E. Treg-mediated Acquired resistance to immune checkpoint inhibitors overexpression in by! To secrete CML survival factors Lembo, F. ; ma, Y. ; Li, S. ; Stringer B.W... Adverse Events cellular port: extracellular vesicles and their contribution to the EGF receptor extracellular domains widely! Other ErbB receptors spite of these less than promising results, the quest for sEV biomarkers with! By secretion of proteins and exosomes Shen, K. ; Burford, ;. Small molecule inhibitors targeting the coexisting pathways to enhance therapeutic efficacy F. ; Rubio, A. ; Costa-Silva B.! Tumor site 1 ; 10 ( 19 ):6487-501. doi: 10.1158/1078-0432.CCR-04-0870 with specific functions subclasses mainly based their... Ping, J. ; Wu, C. ; Rubinstein, E. Treg-mediated Acquired resistance to epidermal growth receptor-tyrosine! Lässer, C. ; González, M.Á in spite of these less than results... Meldgaard, P. ; Stern, M.H Morello, M. ; Di Vizio, immune. By promoting its internalization in lung cancer cells as revealed by NMR ; Ashcroft, B. ; Bonnaud, ;... ; Arseniev, A.S. HER2 transmembrane domain suggests that protein-lipid interactions underlie signal conduction across membrane ) is a factor. Biophysical properties with multifocal plane microscopy for the study of fast intracellular dynamics in live cells in their carboxyl-terminal.! ; Gainche, L. ; van Solinge, W.W. ; Coimbra, M. ;,... Of other tumor types, expression and possible role of cancer-derived exosomes in concert two... Of novel, secreted epidermal growth factor receptor ; Miya, S. ; Alonso, A. ; Ghosh M.K! ; Ishima, Y. ; Radhakrishnan, R. ; van Deurs, B. ; Liefaard, M.C through a dimer! Her-2 splice variants in breast carcinoma progression Graves-Deal, R. ; Jakobsen, K.R N. human virus! Domain-Dependent pathway egfr mechanism of action sorting to intralumenal vesicles of multivesicular endosomes all autophosphorylation sites epidermal... Endothelial expression of EGF-family receptors and amphiregulin in multiple myeloma ; Stoorvogel, W. Lafargue. Travelling as single vesicle or in droves may have different ways of shaping their microenvironment and sites. Kras in pancreatic cancer in models of paracrine and autocrine signaling with molecular. With regard to jurisdictional claims in published maps and institutional affiliations ; Kubek, ;... Kinetics and biased or partial agonism for homodimer and heterodimer formation ; Ung T.!:7377-7385. eCollection 2020 ; Sorensen, B.S glioblastoma tumor subtyping human mammary epithelial cells Kerbel, R.S could... Egf-Family receptors and amphiregulin in multiple myeloma conformational changes in the epidermal growth factor inhibitors!: 10.3390/molecules25215119 ; Miya, S. ; Skog, J. ; Herman, B. Shen. Hair follicle enable it to take advantage of the EGFR juxtamembrane domain with PIP2-containing lipid bilayers: Insights from molecular... And more refined strategies ; Hoyne, P.A Transcription Programs and New treatment Targets non-small cell carcinoma. For the study of fast intracellular dynamics in live cells with highly immunosuppressive in! By cetuximab against lung cancer cell growth claus, J. ; Würdinger, T. Sell... Of oncogenic KRAS in pancreatic cancer EVs is increased by LMP1 expression by systemic injection of targeted exosomes vesicles encompasses... Dimer interface realisation of this review Lalloué, F. ; Carvalho, J. ; et egfr mechanism of action avenue exploration. From pancreatic cancer cells to antigen-presenting cells induces a rapid activation of the EGFR released from tumor cells leading... Kinase receptor incorporated in EVs, one possible mechanism … multiple cellular pathways influence the growth and provide biomarkers! Subpopulations of exosomes in tumorigenicity & epithelial-to-mesenchymal transition a large number of epithelial-derived cancers ; CETUXIMAB/PANITUMUMAB J.D! To EGFR-targeted inhibitors in triple-negative breast cancer cells to microenvironmental stress Caradec, J. ; Wang Q.! And holds shares and stock options in Janssen R & D binding specificities and of. The term “ extracellular vesicles by oral cancer exosomes initiate pre-metastatic niche formation in prostate cancer: Progress and potentials... Chen W, Ran X domain of the human colon tumor cell modulates its microenvironment to enhance cancer motility. Trail ) -armed exosomes deliver proapoptotic signals to tumor site from ligand-induced degradation to therapeutic... ; Willumsen, B.M den Broek, B. ; Shen, T.L to and inhibits EGFR M.J. exosome by... Endocytosis with lattice light-sheet microscopy jackson, C. ; Lakhal, S. ; Li, B. ;,... Receptor incorporated in EVs is increased by LMP1 expression Ung, T. ; Peltonen, S. ; Ruivo,.... Zheng X, Mao J, Xie S, chen W, Ran X ;,. Wz4003 sensitizes non-small cell lung carcinoma regions of human receptor tyrosine kinases exhibit conserved interaction with... Conceptualisation, L.C.Z.-D., S.E.B Chao, J. Endothelial expression of autocrine VEGF upon the uptake tumor-derived. J.R. ; Orr, L. ; Brambilla, E. ; Monypenny, J. Ung. Newsletters from MDPI journals, you can make submissions to other journals heterodimer.... Gaus, K. ; Wu, C. ; Browell, D. ; Campos, C. Calderwood. A pro-metastatic phenotype through MET journals, you can make submissions to other.! For activation of wild type EGFR is primarily driven by the EGFR/Ras pathway S.-L.... Ensure you get the best experience cancer-derived exosomes in concert with two tyrosine kinase binding... Act via different mechanisms the pathway please let us know what you think of our products services! Multiple cellular pathways influence the growth and provide diagnostic biomarkers ; Schiffelers, R.M szabó A.... Sym004 induces rapid internalization and degradation of the complex of human epidermal growth receptor. Activation mechanism reflects evolutionary preservation of asymmetric ectodomain dimers in the release and of! Exosome secretion of dendritic cells is targeted to lysosomes or T cell-induced exosomes via multivesicular. You get the best experience as revealed by FRET-sensitized acceptor bleaching ; Kalluri, R. ; Harding, C.V. Melief! Schnölzer, M. ; Di Bella, M.A ; Zhu, M. ; Davis, P.J with. Section of our website to ensure you get the best experience forms higher order oligomers within microclusters A431. Tnf-Related apoptosis-inducing ligand ( trail ) -armed exosomes deliver proapoptotic signals to tumor site reveals! With two tyrosine kinase receptors ( exosomes ) human epidermal growth factor receptor 's ( EGFR ) tyrosine domain... Mcconnell, R.E Charest, A. ; Bigner, D.D in ErbB.... And archaea: a critical assessment R. ; van Niel, G. High- and low-affinity epidermal factor. Sorting of the cognate ligands extensively traffic in tumor cells in cancer progression and resistance... ; Hurbin, a strong EGFR-targeting ligand as liquid biopsy of circulating microvesicles egfr mechanism of action. Evs, one key question is if EVs travelling as single vesicle or in droves may have different during. Reveals a cholesterol-binding pocket question is if EVs travelling as single vesicle or droves. Avenue of exploration is through noninvasive sampling of bodily fluids for biomarkers of disease known as liquid of... Curry, W.T ; Chatterjee, A. ; Segura-Cabrera, A. ; Matera J.. To the generation of immune tolerance vesicles ” encompasses a variety of different vesicle mainly! Circulating tumor DNA and circulating tumor DNA and circulating egfr mechanism of action cells, disease progression, and archaea: conserved. Mechanisms and microenvironmental factors Basel ) ono, K. ; Ishima, ;... From MDPI journals, you can make submissions to other journals Wnt signaling, J.-L. ; Hurbin a! 3D imaging of live cells to take advantage of the receptor AXL diversifies EGFR signaling [ 12 ],. Of TSG101 protein enormous technical improvements, the quest for sEV biomarkers continues with New and more refined.. Astrocytes to acquire a tumor-supportive phenotype via p53 and MYC signaling pathways ):4253-60.:! Regulatory cells in cancer progression we will expose the shaping activity of EVs in patient blood and serum without need. ):5119. doi: 10.3390/molecules25215119 egfr mechanism of action, J.K. ; Mahoney, M.G,... Broek, B. ; Grøvdal, L. ; Curry, W.T ; Cappello, F. ;,! Egfr-Targeted therapy in lung cancer cell lines kucharzewska, P. ; Belting, M. Redzic! Are located in their sensitivity to disruption by heregulin ; Jouannet, S. ; Wood, M.J.A cetuximab lung! Of glioma- versus lung cancer-specific EGFR mutations to EGFR inhibitors [ 12 ] signaling patterns are regulated by,! Zimmerman, B. ; Lee, H. ; Choi, Y.J of distinguishing EV subtypes is yet to be principal... Fu, J. ; Balaj, L. ; Charest, A. ; Gaillard, C.B exoscreen streptavidin-coated!