2. Academic Validation
  3. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities

Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities

  • Mol Cancer. 2018 Feb 19;17(1):45. doi: 10.1186/s12943-018-0796-y.
Yazhuo Zhang 1 2 3,  Mengfang Xia 1 2 3,  Ke Jin 2,  Shufei Wang 2,  Hang Wei 2,  Chunmei Fan 2,  Yingfen Wu 2,  Xiaoling Li 1 2 3,  Xiayu Li 3,  Guiyuan Li 1 2 3,  Zhaoyang Zeng 4 5 6,  Wei Xiong 7 8 9
Affiliations

Affiliations

  • 1 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2 The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
  • 3 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 4 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
  • 5 The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China. [email protected].
  • 6 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
  • 7 The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
  • 8 The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China. [email protected].
  • 9 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China. [email protected].
PMID: 29455668 DOI: 10.1186/s12943-018-0796-y
Abstract

c-Met is a receptor tyrosine kinase belonging to the MET (MNNG HOS transforming gene) family, and is expressed on the surfaces of various cells. Hepatocyte growth factor (HGF) is the ligand for this receptor. The binding of HGF to c-Met initiates a series of intracellular signals that mediate embryogenesis and wound healing in normal cells. However, in Cancer cells, aberrant HGF/c-Met axis activation, which is closely related to c-Met gene mutations, overexpression, and amplification, promotes tumor development and progression by stimulating the PI3K/Akt, Ras/MAPK, JAK/STAT, Src, Wnt/β-catenin, and other signaling pathways. Thus, c-Met and its associated signaling pathways are clinically important therapeutic targets. In this review, we elaborate on the molecular structure of c-Met and HGF and the mechanism through which their interaction activates the PI3K/Akt, Ras/MAPK, and Wnt signaling pathways. We also summarize the connection between c-Met and RON and EGFR, which are also Receptor Tyrosine Kinases. Finally, we introduce the current therapeutic drugs that target c-Met in primary tumors, and their use in clinical research.

Keywords

EGFR; HGF/c-Met; PI3K/AKT; RON; Ras/MAPK; Therapeutic strategy; Wnt.

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