Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification
2011

Roles of EGFR, HER2, HER3, and RET in Lung Cancer with MET Amplification

publication Evidence: moderate

Author Information

Author(s): Tanizaki J, Okamoto I, Sakai K, Nakagawa K

Primary Institution: Kinki University Faculty of Medicine

Hypothesis

What are the roles and mechanisms of receptor tyrosine kinase heterodimerisation in lung cancer with MET amplification?

Conclusion

Heterodimers of MET with EGFR, HER2, HER3, or RET have different roles in tumor development in lung cancer with MET amplification.

Supporting Evidence

  • EGFR, HER2, HER3, and RET were found to be highly phosphorylated in lung cancer cells with MET amplification.
  • Immunoprecipitation showed that these RTKs form heterodimers exclusively with MET.
  • Depletion of EGFR, HER2, or HER3 induced apoptosis in lung cancer cells.
  • Inhibition of MET kinase activity reduced the extent of RTK heterodimerisation.

Takeaway

This study found that certain proteins work together in lung cancer cells to help them grow and survive, especially when a specific gene is amplified.

Methodology

The study used RTK arrays, immunoprecipitation, annexin V binding, and cell migration assays to investigate the roles of RTKs in lung cancer cells with MET amplification.

Digital Object Identifier (DOI)

10.1038/bjc.2011.322

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