Safaie Qamsari Elmira, Safaei Ghaderi Sepideh, Zarei Bahareh, Dorostkar Ruhollah, Bagheri Salman, Jadidi-Niaragh Farhad, Somi Mohammad Hossein, Yousefi Mehdi
1 Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Tumour Biol. 2017 May;39(5):1010428317699118. doi: 10.1177/1010428317699118.
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.
c-Met（间充质-上皮转化因子）是一种由肝细胞生长因子激活的酪氨酸激酶受体，可调节多种生物学过程，如细胞分散、存活和增殖。c-Met信号异常与多种癌症类型有关，包括结直肠癌。c-Met通过与结直肠癌进展和转移相关的各种机制发生基因改变。特别是在结直肠癌中，存在c-Met信号异常激活的临床前证据。因此，靶向c-Met受体可能是治疗结直肠癌患者的一种有前景的策略。最近，研究还表明，c-Met与其他细胞表面受体之间的相互作用与肿瘤发生和治疗耐药性的发展有关。c-Met与其他受体相互作用促进肿瘤形成和进展的分子机制仍有待探索。本综述将描述结直肠癌中c-Met信号异常的机制，并讨论c-Met受体通过与其他酪氨酸激酶受体和细胞表面蛋白相互作用在结直肠癌中的额外作用。还将讨论针对c-Met通路的新型治疗方法。
