A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Kong LR
PROVIDER: S-EPMC7096530 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.
Kong Li Ren LR Mohamed Salleh Nur Afiqah Binte NAB Ong Richard Weijie RW Tan Tuan Zea TZ Syn Nicholas L NL Goh Robby Miguel RM Fhu Chee Wai CW Tan Daniel S W DSW Iyer N Gopalakrishna NG Kannan Srinivasaraghavan S Verma Chandra S CS Lim Yaw Chyn YC Soo Ross R Ho Jingshan J Huang Yiqing Y Lim Joline S J JSJ Yan Benedict Junrong BJ Nga Min En ME Lim Seng Gee SG Koeffler H Phillip HP Lee Soo Chin SC Kappei Dennis D Hung Huynh The HT Goh Boon Cher BC
Nature communications 20200325 1
c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables MET<sup>N375S</sup> to interact with HER2 in a ligand-independent fashion. The resultant MET<sup>N375S< ...[more]
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