The role of endosomal signaling triggered by metastatic growth factors in tumor progression

• Published in: Cellular signalling Vol. 25; no. 7; pp. 1539 - 1545
• Main Authors: Hu, Chi-Tan, Wu, Jia-Ru, Wu, Wen-Sheng
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.07.2013
• Subjects: Cellular; Disease Progression; Endocytosis; Endosomal signaling; Endosomes - metabolism; Epidermal Growth Factor - physiology; Fibroblast Growth Factors - physiology; Growth factors; Hepatocyte Growth Factor - physiology; Humans; Kinases; Metastatic growth factors; Migration; Neoplasm Metastasis; Neoplasms - metabolism; Neoplasms - pathology; Platelet-Derived Growth Factor - physiology; Progressions; Receptor tyrosine kinase (RTK); Receptors; Regulators; Signal Transduction; Target therapy; Transforming Growth Factor beta - physiology; Tumor metastasis; Tumors; Metastatic growth factors; Receptor tyrosine kinase (RTK); Migration; Target therapy; Endosomal signaling; Tumor metastasis
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2013.03.022

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. •Multiple growth factors induce similar receptor tyrosine kinase (RTK) signaling.•The relationship of RTK endocytosis with signal transduction was well established.•Endosomal signal pathways are promising targets for preventing tumor metastasis.