The HGF/c-Met Axis: A Promising Therapeutic Target in Cancer

About this Research Topic

The HGF/c-Met pathway has been associated with normal development, organ regeneration and cancer. Hepatocyte growth factor (HGF) is the high-affinity ligand for Mesenchymal Epithelial Transition Factor (c-Met), which belongs to the tyrosine kinase receptor family and is predominantly expressed in epithelial cells. Upon binding to biologically active HGF, c-Met undergoes dimerization and recruits downstream signaling effector molecules, including PI3K, PLC-γ1, and STAT3. The downstream signaling pathways include the Ras pathway, PI3K pathway and Wnt/β-catenin signaling pathways, among others. Therefore, the HGF/c-Met axis plays an important role in cell growth, survival and migration and, upon dysregulation, can give rise to a variety of cancerous phenotypes.

Activation of the HGF/c-Met axis is associated with aggressive pathologic features, poor prognosis, and treatment resistance in various tumors. Much attention has been paid to HGF- or c-Met-targeted drugs so as to identify potential therapeutic opportunities. Agents targeting HGF can be categorized into either HGF activation inhibitors (preventing the proteolytic conversion of pro-HGF to its active form) or HGF inhibitors (blocking the binding of HGF to c-MET). Agents targeting the c-MET receptor can be categorized into either c-MET antagonists (binding the receptor) or c-MET tyrosine kinase inhibitors (TKIs), targeting c-MET intracellularly. Further research on the various HGF/c-Met physiological and pathological activities, as well as the elucidation of the pathways mediating them, will contribute to the development of more promising HGF/c-Met axis-based molecules with therapeutic effects.

Therefore, we invite authors to submit original research and review articles that focus on the biological functions and therapeutic potential of the HGF/c-Met axis for cancer. Potential topics include, but are not limited to:

• HGF/c-Met system pathways

• The biochemical characteristics of HGF and c-Met

• The interaction between HGF/c-Met axis and non-coding RNA

• The role of HGF/c-Met in carcinogenesis

• Recent advances in cancer therapies, based on interference with the HGF/c-Met axis

Keywords: HGF, c-Met, biological and pharmacological activity, signaling pathway, non-coding RNA, therapeutic and diagnostic application

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