RRC ID 71956
Author Stern YE, Al-Ghabkari A, Monast A, Fiset B, Aboualizadeh F, Yao Z, Stagljar I, Walsh LA, Duhamel S, Park M.
Title Met-HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells.
Journal Cell Mol Life Sci
Abstract Receptor tyrosine kinases (RTKs) are recognized as targets of precision medicine in human cancer upon their gene amplification or constitutive activation, resulting in increased downstream signal complexity including heterotypic crosstalk with other RTKs. The Met RTK exhibits such reciprocal crosstalk with several members of the human EGFR (HER) family of RTKs when amplified in cancer cells. We show that Met signaling converges on HER3-tyrosine phosphorylation across a panel of seven MET-amplified cancer cell lines and that HER3 is required for cancer cell expansion and oncogenic capacity in vitro and in vivo. Gene expression analysis of HER3-depleted cells identified MPZL3, encoding a single-pass transmembrane protein, as HER3-dependent effector in multiple MET-amplified cancer cell lines. MPZL3 interacts with HER3 and MPZL3 loss phenocopies HER3 loss in MET-amplified cells, while MPZL3 overexpression can partially rescue proliferation upon HER3 depletion. Together, these data support an oncogenic role for a HER3-MPZL3 axis in MET-amplified cancers.
Volume 79(3)
Pages 178
Published 2022-3-5
DOI 10.1007/s00018-022-04149-w
PII 10.1007/s00018-022-04149-w
PMID 35249128
PMC PMC8898245
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism Cell Line, Tumor Cell Proliferation Gene Expression Regulation, Neoplastic Humans Membrane Proteins / antagonists & inhibitors Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Inbred NOD Microsatellite Instability Phosphorylation Protein Isoforms / antagonists & inhibitors Protein Isoforms / genetics Protein Isoforms / metabolism Proto-Oncogene Proteins c-met / genetics Proto-Oncogene Proteins c-met / metabolism* RNA Interference RNA, Small Interfering / metabolism Receptor, ErbB-2 / genetics Receptor, ErbB-2 / metabolism Receptor, ErbB-3 / antagonists & inhibitors Receptor, ErbB-3 / genetics Receptor, ErbB-3 / metabolism* Signal Transduction / genetics Stomach Neoplasms / metabolism Stomach Neoplasms / pathology Transplantation, Heterologous
IF 6.496
Human and Animal Cells EBC-1(RCB1965)