Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon

• DOI: 10.18632/oncotarget.8231
• Publication Date: 2016-03-21T23:45:48Z
• Authors: Juanjuan Xiao; Qiuhong Duan; Zhe Wang; Wei Yan; Huimin Sun; Peipei Xue; Xiaoming Fan; Xiaoyu Zeng; Juan Chen; Chen Shao; Feng Zhu
• Keywords: Male; Mice, Knockout; Mitogen-Activated Protein Kinase Kinases; 0301 basic medicine; Mice, Inbred BALB C; Colon; Protein Stability; Transplantation, Heterologous; Mice, Nude; HCT116 Cells; 3. Good health; 03 medical and health sciences; Cell Transformation, Neoplastic; src-Family Kinases; Cell Line, Tumor; Colonic Neoplasms; Mutation; Animals; Humans; Tyrosine; Phosphorylation; Cells, Cultured; Research Paper

T-LAK cell-originated protein kinase (TOPK), a serine/threonine kinase, is highly expressed in variety of tumors and associated with poor prognosis human malignancies. However, the activation mechanism TOPK still unrevealed. Herein, first we found that Src directly bound phosphorylated at Y74 Y272 vitro. Anti-phospho-TOPK was prepared, endogenous phosphorylation detected colon cancer cells, inhibited cells expressing low levels Src. Subsequently, stably transfected double mutated (TOPK-FF) into JB6 or SW480 observed both anchorage-independent growth ability tumorigenesis TOPK-FF were suppressed compared those wild type (TOPK-WT) ex vivo vivo. The level substrate, Histone H3 Ser10 also decreased dramatically Moreover, showed could inhibit ubiquitination TOPK. Transiently TOPK-WT more stable than pause chase experiment. Endogenous (Src+/+) MEFs knockout (Src-/-). Taken together, our results indicate novel upstream by increases stability activity TOPK, promotes cancer. It may provide opportunities for based targeted therapy patients.