MET normally plays an important role in cell signaling, proliferation, and survival1,2
- MET (mesenchymal-epithelial transition) factor is a receptor tyrosine kinase coded by the MET gene, and is expressed on the surfaces of various epithelial cells3
- When HGF binds to the MET receptor, it activates the downstream pathway and triggers cell growth, proliferation, and survival4
Dysregulation of MET and HGF signaling leads to malignant cellular transformation, proliferation, survival, angiogenesis, invasion, and metastasis3
MET dysregulation can occur through a variety of mechanisms
overexpression
Occurs when there are too many copies of the MET receptor5
The role of MET receptor overexpression is unclear2
An increase in the number of copies of the MET gene6
MET amplification can occur as an oncogenic event or a mechanism of resistance2
METex14
Most commonly caused by splice site alterations2
METex14 is an oncogenic alteration in NSCLC2
MET rearrangement/fusion
A chromosomal rearrangement leading to gene fusion, resulting in a chimeric MET protein7
MET rearrangements/fusions are rare mechanisms, and their role as oncogenic alterations is unclear2
Occurs when there are too many copies of the MET receptor5
The role of MET receptor overexpression is unclear2
amplification
An increase in the number of copies of the MET gene6
MET amplification can occur as an oncogenic event or a mechanism of resistance2
alterations
METex14
Most commonly caused by splice site alterations2
METex14 is an oncogenic alteration in NSCLC2
MET rearrangement/fusion
A chromosomal rearrangement leading to gene fusion, resulting in a chimeric MET protein7
MET rearrangements / fusions are rare mechanisms and their role as oncogenic alterations is unclear2
AKT, protein kinase B; HGF, hepatocyte growth factor; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; mTOR, mechanistic target of rapamycin; NSCLC, non-small cell lung cancer; PI3K, phosphoinositide 3-kinase; RAF, rapidly accelerated fibrosarcoma; STAT 3/5, signal transducer and activator of transcription 3/5.
References
1. Feng Y, Thiagarajan PS, Ma PC. J Thorac Oncol. 2012;7:459-467.2. Drilon A, Cappuzzo F, Ou SI, Camidge DR. J Thorac Oncol. 2016;12(1):15-26.
3. Zhang Y, Xia M, Jin K, et al. Mol Cancer. 2018;1-14.
4. Mo HN, Liu P. Chron Dis Transl Med. 2017;3:148-153.
7. Duplaquet L, Kherrouche Z, Baldacci S, et al. Oncogene. 2018;37:3200-3215.
