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Rsu‐1 (Ras suppressor protein 1) ‐ A potential tumor suppressor in Hepatocellular Carcinoma
Author(s) -
Donthamsetty shashi,
Mars wendy,
Michalopoulos George
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.387.10
Subject(s) - suppressor , cancer research , signal transduction , regulator , biology , hepatocellular carcinoma , cell growth , anti apoptotic ras signalling cascade , cell culture , microbiology and biotechnology , cancer , genetics , gene , mapk/erk pathway
One of the signaling pathways that has been implicated in hepatocellular carcinoma (HCC) development is the Ras pathway. However, Ras mutations are extremely rare in HCC. It is likely that proteins that control this pathway are deregulated/mutated leading to increased activation of Ras signaling. Our lab has shown that 10% of human HCC cases had deletions in Rsu‐1. This protein is known to regulate Ras signaling atleast in mammary tumors and glioblastoma. The present work evaluated the potential role of Rsu‐1 as a tumor suppressor in HCC. Our preliminary data have shown that 1. Rsu‐1 is either absent or downregulated in most human HCC samples. 2. Most of the human HCC cell lines (Hep3B, HepG2, and SNU 449) examined also show down regulation of Rsu‐1 as compared to normal human hepatocytes which is associated with increased Ras activation. The only cell line that had Rsu‐1 levels comparable to human hepatocytes was HUH7 3. Overexpression of Rsu‐1 in HCC cells inhibits cell growth and migration in vitro and 4. Surprisingly, Rsu‐1 does not seem to regulate the activation of Ras; instead, it inhibits the downstream target of Ras called RhoGTPase. Based on these preliminary data Rsu‐1 seems to be a novel regulator of Ras signaling in the hepatocytes and may act as a tumor suppressor by inhibiting the downstream target of Ras signaling pathways called RhoGTPase.