AUTHOR=Hu Xinyue , Tang Feiyu , Liu Peilin , Zhong Taowei , Yuan Fengyan , He Quanyuan , von Itzstein Mark , Li Hao , Weng Liang , Yu Xing TITLE=Structural and Functional Insight Into the Glycosylation Impact Upon the HGF/c-Met Signaling Pathway JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=8 YEAR=2020 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00490 DOI=10.3389/fcell.2020.00490 ISSN=2296-634X ABSTRACT=

Upon interactions with its specific ligand hepatocyte growth factor (HGF), the c-Met signal is relayed to series of downstream pathways, exerting essential biological roles. Dysregulation of the HGF-c-Met signaling pathway has been implicated in the onset, progression and metastasis of various cancers, making the HGF-c-Met axis a promising therapeutic target. Both c-Met and HGF undergo glycosylation, which appears to be biologically relevant to their function and structural integrity. Different types of glycoconjugates in the local cellular environment can also regulate HGF/c-Met signaling by distinct mechanisms. However, detailed knowledge pertaining to the glycosylation machinery of the HGF-c-Met axis as well as its potential applications in oncology research is yet to be established. This mini review highlights the significance of the HGF-c-Met signaling pathway in physiological and pathological context, and discusses the molecular mechanisms by which affect the glycosylation of the HGF-c-Met axis. Owing to the crucial role played by glycosylation in the regulation of HGF/c-Met activity, better understanding of this less exploited field may contribute to the development of novel therapeutics targeting glycoepitopes.