Cks1 regulates human hepatocellular carcinoma cell progression through osteopontin expression

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Title
Cks1 regulates human hepatocellular carcinoma cell progression through osteopontin expression
Author(s)
Yu-Seon Kang; Eun-Jeong Jung; Hyun-Jeong Seok; Seon-Kyu Kim; Jin-Seong Hwang; M L Choi; D G Jo; Yuna Kim; Jinhyeon Choi; Yeo Jin Lee; Eunsun Jung; Jeong Ki Min; Tae Su Han; Jang Seong Kim
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 508, no. 1, pp. 275-281
Publication Year
2019
Abstract
Precise cell cycle regulation is critical to prevent aberrant cell proliferation and cancer progression. Cks1 was reported to be an essential accessory factor for SCFSkp2, the ubiquitin ligase that targets p27Kip1 for proteasomal degradation; these actions drive mammalian cell transition from G1 to S phase. In this study, we investigated the role played by Cks1 in the growth and progression of human hepatocellular carcinoma (HCC) cells. Silencing Cks1 expression abrogated osteopontin (OPN) expression in a p27Kip1-dependent manner in Huh7 HCC cells. OPN increased the proliferation, migration and invasion of Huh7 cells. Pharmacological inhibitor studies demonstrated that ERK1/2 signaling is responsible mainly for Cks1-mediated OPN expression. Cks1 appears to regulate ERK1/2 signaling through the expression of dual-specificity phosphatase 16 (DUSP16) because both Cks1 knockdown, which leads to DUSP16 upregulation, and DUSP16 overexpression decreased ERK1/2 phosphorylation and the resulting OPN expression. The same is true for the Cks1-mediated increases in p27Kip1, suggesting that Cks1 regulates OPN expression through activating ERK1/2 signaling either by suppressing DUSP16 expression or by a p27Kip1-dependent mechanism. Cks1 and OPN expression levels were significantly higher, but DUSP16 expression levels were significantly lower in HCC tissues than in normal liver tissues. Both Cks1 and OPN expression were negatively correlated with DUSP16 expression, whereas Cks1 expression was positively correlated with OPN expression. Moreover, combined panels for the expression levels of Cks1, DUSP16 and OPN showed significant prognostic power for the risk assessment of HCC patient overall survival. In conclusion, our data propose a novel function for Cks1 as a tumor promoter through the expression of the strongly oncogenic protein OPN in HCC.
Keyword
Cks1DUSP16Hepatocellular carcinomaOsteopontinp27(Kip1)
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2018.11.070
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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