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Mol Cell Biochem. 2013 Jul;379(1-2):191-9. doi: 10.1007/s11010-013-1641-7. Epub 2013 May 6.

SRPK1 contributes to malignancy of hepatocellular carcinoma through a possible mechanism involving PI3K/Akt.

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1
Key Laboratory of Systems Biomedicine (Ministry of Education) of Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Protein kinases are important regulators in biologic processes. Aberrant expression of protein kinases often causes diseases including cancer. In the present study, we found that the serine-arginine protein kinase 1 (SRPK1) might be involved in hepatocellular carcinoma (HCC) proliferation from a kinome screen using a loss-of-function approach. In clinical samples, SRPK1 was frequently up-regulated in HCCs as compared with adjacent non-tumor tissues at both mRNA and protein levels. Functional studies indicated that overexpression of wild-type SRPK1 promoted HCC cell proliferation, while forced expression of the kinase-dead mutant of SRPK1 or RNA interference against SRPK1 suppressed cell growth and malignancy as measured in soft agar assay. The kinase-dead mutant of SRPK1 also inhibited subcutaneous xenografts' growth of HCC cells in nude mice. Furthermore, western bolt analysis showed overexpression of wild-type SRPK1 enhanced Akt phosphorylation and knockdown of SRPK1 by RNA interference attenuated Akt phosphorylation induced by epidermal growth factor. Meanwhile, overexpression of wild-type SRPK1 also induced a concurrent increase in the total tyrosine phosphorylation of phosphotidylinositol-3 kinase p110α subunit, indicating a functional link between SRPK1 and PI3K/Akt signaling. Our findings suggest that SRPK1 plays an oncogenic role and could be a potential therapeutic target in HCC.

PMID:
23644876
DOI:
10.1007/s11010-013-1641-7
[Indexed for MEDLINE]
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