Regulation of MET receptor signaling by SOCS1 and its implications for hepatocellular carcinoma.
The SOCS1 gene is a frequent target of epigenetic repression in hepatocellular carcinoma. Many other types of cancer also harbor methylated SOCS1 gene. Besides, recent studies implicate microRNAs targeting SOCS1 in cancer progression. These findings suggest a broad tumor suppressor role of SOCS1 and have stimulated the quest to elucidate the underlying molecular mechanisms. The essential physiological function of SOCS1 is to attenuate interferon gamma signaling in immune cells. SOCS1 binds activated JAK kinases and the receptor chains of several cytokines, some of which are implicated in cancer progression. SOCS1 also facilitates ubiquitination and proteasomal degradation of many signaling molecules downstream of cytokine and growth factor receptors. We have shown that SOCS1 inhibits signaling via the hepatocyte growth factor receptor c-MET in hepatocytes. Aberrant MET signaling, implicated in the progression of many types of cancers, also contributes to the development of chemoresistance to tyrosine kinase inhibitors and drugs targeting other oncogenic signaling pathways. Here, we discuss the SOCS1-dependent regulation of MET signaling as an important mechanism underlying the tumor suppressor role of SOCS1 that is relevant not only to hepatocellular carcinoma but also to other types of cancers.
Yirui
Y
Gui
Mehdi
M
Yeganeh
Yuneivy
Y
Cepero-Donates
Sheela
S
Ramanathan
Caroline
C
Saucier
Immunology division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, 3001 North 12th avenue, Sherbrooke QC J1H 5N4, Canada. Subburaj.Ilangumaran@Usherbrooke.ca.
Subburaj
S
Ilangumaran
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D035683:MicroRNAs; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018121:Receptors, Cytokine / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D054875:Ubiquitination
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D018121:Receptors, Cytokine; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019859:Proto-Oncogene Proteins c-met