The MET (Mesenchymal Epithelial Transition) gene encodes a prototypical receptor tyrosine kinase, which is involved in the tyrosine kinase signaling pathway that regulates cell motility, survival, proliferation, invasion, and metastasis in many cancers. In this article, we review the hottest oncogene MET, hoping to give you insights on its role in cancer development as a therapeutic target in lung cancer research.


Overview of MET Gene

MET known as c-MET, is a proto-oncogene, which is located in the long arm of human chromosome 7 and contains 21 exons. MET is a tyrosine kinase receptor of hepatocyte growth factor (HGF), which mainly includes three domains: extracellular domain, the transmembrane domain and intracellular domain. The combination of HGF and c-MET will activate MET and then activates numerous downstream signaling pathways, such as PI3K Akt, RAS MAPK, stat, and Wnt/Wnt/β-catenin. Therefore, MET exerts its effects of promoting cell proliferation, cell growth, cell migration, invasion, angiogenesis and plays a key role in normal tissue development and tumor progression. When the expression of the c-MET pathway is normal, it promotes the differentiation and repair of tissue. While disorders occur in the MET gene, it promotes tumor cell proliferation and metastasis.


Figure 1. HGF signaling pathway. The binding of activated HGF to MET receptor can induce the activation of MET tyrosine kinase and the autophosphorylation of tyrosine residues in MET. The activation of c-MET by HGF can lead to a variety of cell signaling-mediated tumor growth, metastasis, and angiogenesis. The binding of HGF with c-MET can induce the phosphorylation of tyrosine residues in the C-terminal cluster of tyrosine kinases, leading to a variety of cellular biological activities, including mitogenesis and more. HGF/MET signal transduction activates multiple signal transduction pathways, such as PI3K Akt, RAS MAPK, stat and Wnt/ β- Catenin et al.


MET gene and Tumor Development

The disorder of the MET pathway in oncology is manifested in several ways: genetic mutation, amplification, rearrangement, or overexpression of proteins. In addition to non-small cell lung cancer (NSCLC), breast cancer, colon cancer, renal cell carcinoma and gastric cancer all overexpress MET. In addition, MET amplification was found in colon cancer, esophageal cancer and gastric cancer. Blocking the HGF/c-MET signaling pathway can effectively inhibit tumor development and metastasis.


Therapy targeting MET in non-small cell lung cancer (NSCLC)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide with a poor prognosis. Although NSCLC research progress has been striking in terms of detection and treatment of the abnormal MET pathway type, there are few drugs targeting c-MET that are available. While the MET gene mutation not only leads to primary lung cancer, it is also a major cause of anti-lung cancer drug resistance, which is a driver gene in lung cancer. Anti-MET therapies are divided into selective TK and non-selective (also known as multi-target) TKI and antibodies against MET or its ligand HGF. According to its binding mechanism and conformation, TKI can be classified into three types. TKI type I and II are competitive MET inhibitors of ATP, but they have different selectivity, conformation, and binding sites. These two categories include most of the TKIs currently in use or under development, such as crizotinib, camatinib and savolitinib (type I) or cabatinib, crestinib and glitinib (type II). Tivantinib is an exception because its activity is only partially related to MET inhibition (with non-ATP competitive binding, involving other mechanisms). Type III TKI binds to allosteric sites different from ATP binding sites. At present, no type III inhibitors have been developed for oncology.


The MET gene (and its encoded protein) has become one of the hottest research targets in the field of cancer. The approval of MET inhibitors is of revolutionary significance for medical researchers and patients with NSCLC. Teotinib is currently listed in Japan and the United States. We expect MET inhibitors to continue bringing good news to more patients, quickly progressing so that more cancer patients can benefit from targeted therapy.


The mouse tumor model is an essential tool to study the mechanism of tumor development, drug screening and efficacy evaluation. Cyagen can provide a variety of non-small cell lung cancer related gene editing mice including Met, Stk4, Alk, Eml4, Rassf5, Fhit, and more.

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In vivo tumor models, such as cell line-derived tumor xenograft (CDX) and syngeneic models, play an important role in basic research of tumorigenesis and metastasis, as well as drug development and treatment.

Cyagen can provide you with various CDX and syngeneic tumor models, such as breast cancer, liver cancer, colon cancer, melanoma, lung cancer, and brain cancer models, as well as highly customized in vivo pharmacodynamic services for the corresponding models.

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1. Yap TA, et al. (2010) Targeting the hgf/c-MET axis: State of play. Mol Cancer Ther 9(5), 1077-1079.

2. Bylicki O, Paleiron N, Assié JB, Chouaïd C. Targeting the MET-Signaling Pathway in Non-Small–Cell Lung Cancer: Evidence to Date. Onco Targets Ther. 2020;13:5691-5706.

3. Organ SL, Tsao M-S. An overview of the c-MET signaling pathway. Therapeutic Advances in Medical Oncology. November 2011:S7-S19.