The Met tyrosine kinase receptor as a therapeutic target and a potential cancer stem cell factor responsible for therapy resistance (Review).

ABSTRACT

The MET tyrosine kinase receptor plays an important role during tumor development and progression being responsible for proliferation, morphogenetic transformation, cell motility and invasiveness. High expression of the MET receptor has been shown to correlate with increased tumor growth and metastasis, poor prognosis and resistance to radiotherapy. Moreover, MET expression and activation has been shown to be associated with therapy resistance. The occurrence of resistance to targeted therapy might be related to the presence of cancer stem cells (CSCs). CSCs are a subpopulation of cells in the tumor that possess the ability of self-renewal, clonogenicity, radioresistance and self-sustained protection from apoptosis. Recently, MET has been postulated as an essential factor supporting the functional stem cell phenotype in some tumors and as a CSC factor is believed to be responsible for therapy resistance. This review presents the results from recent studies identifying MET as a potential marker of CSCs and tumor initiating cells, demonstrating pivotal role of MET in supporting stem cell phenotype and indicating the role of MET in acquiring resistance to antitumor therapy.