Format

Send to

Choose Destination
Br J Cancer. 2011 Sep 6;105(6):807-13. doi: 10.1038/bjc.2011.322. Epub 2011 Aug 16.

Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification.

Author information

1
Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.

Abstract

BACKGROUND:

MET is a receptor tyrosine kinase (RTK) whose gene is amplified in various tumour types. We investigated the roles and mechanisms of RTK heterodimerisation in lung cancer with MET amplification.

METHODS:

With the use of an RTK array, we identified phosphorylated RTKs in lung cancer cells with MET amplification. We examined the roles and mechanisms of action of these RTKs with immunoprecipitation, annexin V binding, and cell migration assays.

RESULTS:

We identified epidermal growth factor receptor (EGFR), human EGFR (HER)2, HER3, and RET in addition to MET as highly phosphorylated RTKs in lung cancer cells with MET amplification. Immunoprecipitation revealed that EGFR, HER2, HER3, and RET each formed a heterodimer exclusively with MET and that these associations were markedly reduced in extent by treatment with a MET kinase inhibitor. RNA interference-mediated depletion of EGFR, HER2, or HER3 induced apoptosis in association with inhibition of AKT and ERK signalling pathways, whereas depletion of HER2 or RET inhibited both cell migration and STAT3 signalling.

CONCLUSION:

Our data suggest that heterodimers of MET with EGFR, HER2, HER3, or RET have differential roles in tumour development, and they provide new insight into the function of trans-phosphorylated RTKs as heterodimerisation partners of MET in lung cancer with MET amplification.

PMID:
21847121
PMCID:
PMC3171021
DOI:
10.1038/bjc.2011.322
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center