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Reptin regulates insulin‐stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP‐1/PTPN6
Author(s) -
Raymond AnneAurélie,
Javary Joaquim,
Breig Osman,
Neaud Véronique,
Rosenbaum Jean
Publication year - 2017
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3274
Subject(s) - protein kinase b , phosphorylation , pi3k/akt/mtor pathway , downregulation and upregulation , insulin receptor , insulin , medicine , cancer research , protein tyrosine phosphatase , tyrosine phosphorylation , biology , endocrinology , microbiology and biotechnology , insulin resistance , signal transduction , biochemistry , gene
Hepatocellular carcinoma (HCC) is the main primary cancer of the liver. Many studies have shown that insulin resistance is a risk factor for HCC. We previously discovered the overexpression and oncogenic role of the Reptin/RUVBL2 ATPase in HCC. Here, we found that Reptin silencing enhanced insulin sensitivity in 2 HCC cell lines, as shown by a large potentiation of insulin‐induced AKT phosphorylation on Ser473 and Thr308, and of downstream signalling. Reptin silencing did not affect the tyrosine phosphorylation of the insulin receptor nor of IRS1, but it enhanced the tyrosine phosphorylation of the p85 subunit of PI3K. The expression of the SHP‐1/PTPN6 phosphatase, which dephosphorylates p85, was reduced after Reptin depletion. Forced expression of SHP‐1 restored a normal AKT phosphorylation after insulin treatment in cells where Reptin was silenced, demonstrating that the downregulation of SHP1 is mechanistically linked to increased Akt phosphorylation. In conclusion, we have uncovered a new function for Reptin in regulating insulin signalling in HCC cells via the regulation of SHP‐1 expression. We suggest that the regulation of insulin sensitivity by Reptin contributes to its oncogenic action in the liver.