The c-Met receptor: Implication for targeted therapies in colorectal cancer
Elmira Safaie Qamsari1,2, Sepideh Safaei Ghaderi3,4,
Bahareh Zarei5, Ruhollah Dorostkar6, Salman Bagheri1,2,
Farhad Jadidi-Niaragh1,2,7, Mohammad Hossein Somi8
and Mehdi Yousefi8
c-Met (mesenchymal–epithelial transition factor) is a tyrosine kinase receptor activated by hepatocyte growth factor and regulates multiple biological processes, such as cell scattering, survival, and proliferation. Aberrant c-Met signaling has been implicated in a variety of cancer types, including colorectal cancer. c-Met is genetically altered through various mechanisms that is associated with colorectal cancer progression and metastasis. Especially, in colorectal cancer, preclinical evidence for the aberrant activation of the c-Met signaling exists. Accordingly, molecular targeting of c-Met receptor could be a promising strategy, in the treatment of colorectal cancer patients. Recently, it was also shown that crosstalk between c-Met and other cell surface receptors attributes to tumorigenesis and development of therapeutic resistance. Characterization of the molecular mechanisms through which c-Met crosstalks with other receptors in favor of tumor formation and progression remains to explore. This review will describe the mechanisms of aberrant c-Met signaling in colorectal cancer and discuss on additional roles for c-Met receptor through crosstalk with other tyrosine kinase receptors and cell surface proteins in colorectal cancer. Novel therapeutic approaches for c-Met pathway targeting will also be discussed.