Transforming properties of MET receptor exon 14 skipping can be recapitulated by loss of the CBL ubiquitin ligase binding site.
MET Ex14
lung cancer
receptor tyrosine kinase
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
07
06
2023
received:
19
01
2023
accepted:
19
06
2023
medline:
26
9
2023
pubmed:
20
7
2023
entrez:
19
7
2023
Statut:
ppublish
Résumé
MET is a receptor tyrosine kinase that is activated in many cancers through various mechanisms. MET exon 14 (Ex14) skipping occurs in 3% of nonsmall cell lung tumors. However, the contribution of the regulatory sites lost upon this skipping, which include a phosphorylated serine (S985) and a binding site for the E3 ubiquitin ligase CBL (Y1003), remains elusive. Sequencing of 2808 lung tumors revealed 71 mutations leading to MET exon 14 skipping and three mutations affecting Y1003 or S985. In addition, MET exon 14 skipping and MET Y1003F induced similar transcriptional programs, increased the activation of downstream signaling pathways, and increased cell mobility. Therefore, the MET Y1003F mutation is able to fully recapitulate responses induced by MET exon 14 skipping, suggesting that loss of the CBL binding site is the main contributor of cell transformation induced by MET Ex14 mutations.
Identifiants
pubmed: 37468447
doi: 10.1002/1873-3468.14702
doi:
Substances chimiques
Proto-Oncogene Proteins c-met
EC 2.7.10.1
Ubiquitins
0
Ligases
EC 6.-
Banques de données
RefSeq
['NM_000245.3', 'NM_001127500.3']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2301-2315Informations de copyright
© 2023 Federation of European Biochemical Societies.
Références
Yamaoka T, Kusumoto S, Ando K, Ohba M and Ohmori T (2018) Receptor tyrosine kinase-targeted cancer therapy. Int J Mol Sci 19, 3491.
Skoulidis F and Heymach JV (2019) Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy. Nat Rev 19, 495-509.
Politi K and Herbst RS (2015) Lung cancer in the era of precision medicine. Clin Cancer Res 21, 2213-2220.
Ponzetto C, Giordano S, Peverali F, Della Valle G, Abate ML, Vaula G and Comoglio PM (1991) c-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. Oncogene 6, 553-559.
Watermann I, Schmitt B, Stellmacher F, Muller J, Gaber R, Kugler C, Reinmuth N, Huber RM, Thomas M, Zabel P et al. (2015) Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation? Diagn Pathol 10, 130.
Yang Y, Wu N, Shen J, Teixido C, Sun X, Lin Z, Qian X, Zou Z, Guan W, Yu L et al. (2015) MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer. Gastric Cancer 19, 778-788.
Koochekpour S, Jeffers M, Rulong S, Taylor G, Klineberg E, Hudson EA, Resau JH and Vande Woude GF (1997) Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res 57, 5391-5398.
Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P, Scherer SW, Zhuang Z, Lubensky I, Dean M et al. (1997) Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 16, 68-73.
Duplaquet L, Kherrouche Z, Baldacci S, Jamme P, Cortot AB, Copin MC and Tulasne D (2018) The multiple paths towards MET receptor addiction in cancer. Oncogene 37, 3200-3215.
Birchmeier C, Birchmeier W, Gherardi E and Vande Woude GF (2003) Met, metastasis, motility and more. Nat Rev Mol Cell Biol 4, 915-925.
Bladt F, Riethmacher D, Isenmann S, Aguzzi A and Birchmeier C (1995) Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature 376, 768-771.
Schmidt C, Bladt F, Goedecke S, Brinkmann V, Zschiesche W, Sharpe M, Gherardi E and Birchmeler C (1995) Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373, 699-702.
Uehara Y, Minowa O, Mori C, Shlota K, Kuno J, Noda T and Kitamura N (1995) Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 373, 702-705.
Maina F, Hilton MC, Ponzetto C, Davies AM and Klein R (1997) Met receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neurons. Genes Dev 11, 3341-3350.
Borowiak M, Garratt AN, Wustefeld T, Strehle M, Trautwein C and Birchmeier C (2004) Met provides essential signals for liver regeneration. Proc Natl Acad Sci USA 101, 10608-10613.
Huh CG, Factor VM, Sanchez A, Uchida K, Conner EA and Thorgeirsson SS (2004) Hepatocyte growth factor/c-met signaling pathway is required for efficient liver regeneration and repair. Proc Natl Acad Sci USA 101, 4477-4482.
Chmielowiec J, Borowiak M, Morkel M, Stradal T, Munz B, Werner S, Wehland J̈, Birchmeier C and Birchmeier W (2007) c-met is essential for wound healing in the skin. J Cell Biol 177, 151-162.
Calvi C, Podowski M, Lopez-Mercado A, Metzger S, Misono K, Malinina A, Dikeman D, Poonyagariyon H, Ynalvez L, Derakhshandeh R et al. (2013) Hepatocyte growth factor, a determinant of airspace homeostasis in the murine lung. PLoS Genet 9, e1003228.
The Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543-550.
Descarpentries C, Lepretre F, Escande F, Kherrouche Z, Figeac M, Sebda S, Baldacci S, Grégoire V, Jamme P, Copin M-C et al. (2018) Optimization of routine testing for MET exon 14 splice site mutations in NSCLC patients. J Thorac Oncol 13, 1873-1883.
Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, Akimov M, Bufill JA, Lee C, Jentz D et al. (2015) Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 5, 850-859.
Cortot AB, Kherrouche Z, Descarpentries C, Wislez M, Baldacci S, Furlan A and Tulasne D (2017) Exon 14 deleted MET receptor as a new biomarker and target in cancers. J Natl Cancer Inst 109, djw262.
Paik P, Cortot A, Felip E, Sakai H, Mazieres J, Horn L, Griesinger F, Bruns R, Scheele J, Straub J et al. (2020) A phase II trial of tepotinib in patients with non-small cell lung cancer (NSCLC) harboring MET alterations: the VISION study. Ann Oncol 30, ii66.
Wolf J, Seto T, Han J-Y, Reguart N, Garon EB, Groen HJM, Tan DSW, Hida T, de Jonge M, Orlov SV et al. (2020) Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med 383, 944-957.
Gandino L, Longati P, Medico E, Prat M and Comoglio PM (1994) Phosphorylation of serine 985 negatively regulates the hepatocyte growth factor receptor kinase. J Biol Chem 269, 1815-1820.
Nakayama M, Sakai K, Yamashita A, Nakamura T, Suzuki Y and Matsumoto K (2013) Met/HGF receptor activation is regulated by juxtamembrane Ser985 phosphorylation in hepatocytes. Cytokine 62, 446-452.
Tulasne D, Deheuninck J, Lourenco FC, Lamballe F, Ji Z, Leroy C, Puchois E, Moumen A, Maina F, Mehlen P et al. (2004) Proapoptotic function of the MET tyrosine kinase receptor through caspase cleavage. Mol Cell Biol 24, 10328-10339.
Foveau B, Leroy C, Ancot F, Deheuninck J, Ji Z, Fafeur V and Tulasne D (2007) Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor. Cell Death Differ 14, 752-764.
Lefebvre J, Muharram G, Leroy C, Kherrouche Z, Montagne R, Ichim G, Tauszig-Delamasure S, Chotteau-Lelievre A, Brenner C, Mehlen P et al. (2013) Caspase-generated fragment of the met receptor favors apoptosis via the intrinsic pathway independently of its tyrosine kinase activity. Cell Death Dis 4, e871.
Duplaquet L, Leroy C, Vinchent A, Paget S, Lefebvre J, Vanden Abeele F, Lancel S, Giffard F, Paumelle R, Bidaux G et al. (2020) Control of cell death/survival balance by the MET dependence receptor. Elife 9, e50041.
Peschard P, Ishiyama N, Lin T, Lipkowitz S and Park M (2004) A conserved DpYR motif in the juxtamembrane domain of the met receptor family forms an atypical c-Cbl/Cbl-b tyrosine kinase binding domain binding site required for suppression of oncogenic activation. J Biol Chem 279, 29565-29571.
Peschard P, Fournier TM, Lamorte L, Naujokas MA, Band H, Langdon WY and Park M (2001) Mutation of the c-Cbl TKB domain binding site on the met receptor tyrosine kinase converts it into a transforming protein. Mol Cell 8, 995-1004.
Abella JV, Peschard P, Naujokas MA, Lin T, Saucier C, Urbe S and Park M (2005) Met/hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation. Mol Cell Biol 25, 9632-9645.
Deheuninck J, Goormachtigh G, Foveau B, Ji Z, Leroy C, Ancot F, Villeret V, Tulasne D and Fafeur V (2009) Phosphorylation of the MET receptor on juxtamembrane tyrosine residue 1001 inhibits its caspase-dependent cleavage. Cell Signal 21, 1455-1463.
Champagnac A, Bringuier P-P, Barritault M, Isaac S, Watkin E, Forest F, Maury JM, Girard N and Brevet M (2020) Frequency of MET exon 14 skipping mutations in non-small cell lung cancer according to technical approach in routine diagnosis: results from a real-life cohort of 2,369 patients. J Thorac Dis 12, 2172-2178.
Miao YL and Xu QQ (2019) MET Y1003S point mutation shows sensitivity to crizotinib in a patient with lung adenocarcinoma. Lung Cancer 130, 84-86.
Menyhárt O, Harami-Papp H, Sukumar S, Schäfer R, Magnani L, de Barrios O and Győrffy B (2016) Guidelines for the selection of functional assays to evaluate the hallmarks of cancer. Biochim Biophys Acta 1866, 300-319.
Hanahan D and Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674.
Gao B and Zeng R (2021) Case report: a 91-year-old patient with non-small cell lung cancer harboring MET Y1003S point mutation. Front Med (Lausanne) 8, 772998.
Wiesweg M, Herold T, Metzenmacher M, Eberhardt WE, Reis H, Darwiche K, Aigner C, Stuschke M, Herrmann K, Nensa F et al. (2020) Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation. Lung Cancer 139, 165-168.
Davies KD, Lomboy A, Lawrence CA, Yourshaw M, Bocsi GT, Camidge DR and Aisner DL (2019) DNA-based versus RNA-based detection of MET exon 14 skipping events in lung cancer. J Thorac Oncol 14, 737-741.
O'Brien O, Wright MC, O'Brien C, Geoghegan O, Leonard N, Nicholson S, Cuffe S, Fabre A, Jochum W, Joerger M et al. (2019) Cost-efficient and easy to perform PCR-based assay to identify met exon 14 skipping in formalin-fixed paraffin-embedded (FFPE) non-small cell lung cancer (NSCLC) samples. Diagnostics (Basel) 9, 13.
Cerqua M, Botti O, Arigoni M, Gioelli N, Serini G, Calogero R, Boccaccio C, Comoglio PM and Altintas DM (2022) MET∆14 promotes a ligand-dependent, AKT-driven invasive growth. Life Sci Alliance 5, e202201409.
Lee J-H, Gao CF, Lee CC, Kim MD and Woude GFV (2006) An alternatively spliced form of met receptor is tumorigenic. Exp Mol Med 38, 565-573.
Kong-Beltran M, Seshagiri S, Zha J, Zhu W, Bhawe K, Mendoza N, Holcomb T, Pujara K, Stinson J, Fu L et al. (2006) Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res 66, 283-289.
Togashi Y, Mizuuchi H, Tomida S, Terashima M, Hayashi H, Nishio K and Mitsudomi T (2015) MET gene exon 14 deletion created using the CRISPR/Cas9 system enhances cellular growth and sensitivity to a MET inhibitor. Lung Cancer 90, 590-597.
Lu X, Peled N, Greer J, Wu W, Choi P, Berger AH, Wong S, Jen KY, Seo Y, Hann B et al. (2017) MET exon 14 mutation encodes an actionable therapeutic target in lung adenocarcinoma. Cancer Res 77, 4498-4505.
Wang F, Liu Y, Qiu W, Shum E, Feng M, Zhao D, Zheng D, Borczuk A, Cheng H and Halmos B (2022) Functional analysis of MET exon 14 skipping alteration in cancer invasion and metastatic dissemination. Cancer Res 82, 1365-1379.
Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N and Martinez-Fierro ML (2020) The roles of matrix metalloproteinases and their inhibitors in human diseases. Int J Mol Sci 21, 9739.
Tanimura S, Asato K, Fujishiro S and Kohno M (2003) Specific blockade of the ERK pathway inhibits the invasiveness of tumor cells: down-regulation of matrix metalloproteinase-3/-9/-14 and CD44. Biochem Biophys Res Commun 304, 801-806.
Genersch E, Hayess K, Neuenfeld Y and Haller H (2000) Sustained ERK phosphorylation is necessary but not sufficient for MMP-9 regulation in endothelial cells: involvement of Ras-dependent and -independent pathways. J Cell Sci 113, 4319-4330.
Yang C-Q, Li W, Li S-Q, Li J, Li Y-W, Kong S-X, Liu RM, Wang SM and Lv WM (2014) MCP-1 stimulates MMP-9 expression via ERK 1/2 and p38 MAPK signaling pathways in human aortic smooth muscle cells. Cell Physiol Biochem 34, 266-276.