title: The role of endosomal signaling triggered by metastatic growth factors in tumor progression.
abstract: Within tumor microenvironment, a lot of growth factors such as hepatocyte growth factor and epidermal growth factor may induce similar signal cascade downstream of receptor tyrosine kinase (RTK) and trigger tumor metastasis synergistically. In the past decades, the intimate relationship of RTK-mediated receptor endocytosis with signal transduction was well established. In general, most RTK undergoes clathrin-dependent endocytosis and/or clathrin-independent endocytosis. The internalized receptors may sustain the signaling within early endosome, recycling to plasma membrane for subsequent ligand engagement or sorting to late endosomes/lysosome for receptor degradation. Moreover, receptor endocytosis influences signal transduction in a temporal and spatial manner for periodical and polarized cellular processes such as cell migration. The endosomal signalings triggered by various metastatic factors are quite similar in some critical points, which are essential for triggering cell migration and tumor progression. There are common regulators for receptor endocytosis including dynamin, Rab4, Rab5, Rab11 and Cbl. Moreover, many critical regulators within the RTK signal pathway such as Grb2, p38, PKC and Src were also modulators of endocytosis. In the future, these may constitute a new category of targets for prevention of tumor metastasis.
authors.affiliation: Research Centre for Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Chi-Tan
authors.initials: CT
authors.lastname: Hu
authors.forename: Jia-Ru
authors.initials: JR
authors.lastname: Wu
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Wu
mesh_terms: D018450:Disease Progression; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C066855:HGF protein, human; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor