title: SRPK1 contributes to malignancy of hepatocellular carcinoma through a possible mechanism involving PI3K/Akt.
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.
authors: Key Laboratory of Systems Biomedicine (Ministry of Education) of Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Bo
authors: B
authors: Zhou
authors: Yandong
authors: Y
authors: Li
authors: Qing
authors: Q
authors: Deng
authors: Haixiao
authors: H
authors: Wang
authors: Yuping
authors: Y
authors: Wang
authors: Bing
authors: B
authors: Cai
authors: Ze-Guang
authors: ZG
authors: Han
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C087728:SRPK1 protein, human
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