Title:Regulation of MET Receptor Signaling by SOCS1 and its Implications for Hepatocellular Carcinoma
Volume: 20
Issue: 17
Author(s): Yirui Gui, Mehdi Yeganeh, Yuneivy Cepero-Donates, Sheela Ramanathan, Caroline Saucier and Subburaj Ilangumaran
Affiliation:
Keywords:
SOCS1, epigenetic repression, hepatocyte, hepatocellular carcinoma, MET, oncogenic signaling.
Abstract: 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.
