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• W2912197884 abstract "Serine/arginine protein‐specific kinase 2 ( SRPK 2) plays a vital role in the progression of a range of different malignancies, including pancreatic cancer. However, the mechanisms are poorly understood. Previous studies have shown that in hepatocellular carcinoma, SRPK 2 knockdown leads to the upregulation of the cell fate determining protein Numb, and in pancreatic cancer cells, Numb knockdown prevents ubiquitin‐mediated degradation of p53. In this study, we investigated the relationship between SRPK 2, Numb and p53 in the development of pancreatic cancer with or without chemical agent treatment in vitro . SRPK 2 expression was upregulated in pancreatic cancer tissues and associated with decreased overall survival in pancreatic cancer patients, indicating that expression of this protein can be used as a marker of unfavourable prognosis. Expression of SRPK 2 was positively associated with tumour T stage and Union for International Cancer Control ( UICC ) stage, and negatively associated with Numb expression in serial tissue sections. In pancreatic cancer cells, SRPK 2 downregulation or overexpression led to modulation of Numb and wild‐type p53 protein expression in response to oxaliplatin treatment. Furthermore, these three endogenous proteins could be coimmunoprecipitated as a triple complex. Numb or p53 knockdown reversed the upregulation of p53 that was induced by silencing SRPK 2. SRPK 2 overexpression promoted cell invasion and migration, and decreased chemosensitivity of cancer cells to gemcitabine or oxaliplatin treatment. Conversely, SRPK 2 silencing decreased cell invasion and migration and increased chemosensitivity; these effects were reversed by silencing p53 in oxaliplatin‐treated pancreatic cancer cells. Our data suggest that SRPK 2 negatively regulates p53 by downregulating Numb under chemical agent treatment. Thus, SRPK 2 promotes the development and progression of pancreatic cancer in a p53‐dependent manner." @default.
• W2912197884 created "2019-02-21" @default.
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• W2912197884 date "2019-03-01" @default.
• W2912197884 modified "2023-10-01" @default.
• W2912197884 title "Serine/arginine protein‐specific kinase 2 promotes the development and progression of pancreatic cancer by downregulating Numb and p53" @default.
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• W2912197884 doi "https://doi.org/10.1111/febs.14778" @default.
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