Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer.

Abstract

Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

• Authors: Guosen Wang, Weiwei Sheng, Jingtong Tang, Xin Li, Jianping Zhou, Ming Dong
• Journal: Bioscience reports (Biosci Rep) Vol. 40 Issue 1 (01 31 2020) ISSN: 1573-4935 [Electronic] England
• PMID: 31898732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s).

Chemical References

• Membrane Proteins
• Nerve Tissue Proteins
• NUMB protein, human
• TP53 protein, human
• Tumor Suppressor Protein p53
• Protein Serine-Threonine Kinases
• SRPK2 protein, human
• Cisplatin
• Fluorouracil

Topics

• Cell Line, Tumor
• Cell Movement (drug effects, physiology)
• Cell Proliferation (drug effects, physiology)
• Cisplatin (pharmacology)
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Disease Progression
• Female
• Fluorouracil (pharmacology)
• HCT116 Cells
• Humans
• Male
• Membrane Proteins (metabolism)
• Middle Aged
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Staging (methods)
• Nerve Tissue Proteins (metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Signal Transduction (drug effects, physiology)
• Tumor Suppressor Protein p53 (metabolism)