| 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
|
| Resource |
| Human and Animal Cells |
EBC-1(RCB1965) |
