Synaptopodin-2 promotes hepatocellular carcinoma metastasis via calcineurin-induced nuclear-cytoplasmic translocation. (10th July 2020)

• Record Type: Journal Article
• Authors: Gao, Jie; Zhang, Hua-Peng; Sun, Yao-Hui; Guo, Wen-Zhi; Li, Jie; Tang, Hong-Wei; Guo, Dan-Feng; Zhang, Jia-Kai; Shi, Xiao-Yi; Yu, Dong-Sheng; Zhang, Xiao-Dan; Wen, Pei-Hao; Shi, Jia-Hua; Zhang, Shui-Jun
• Is Part Of: Cancer letters. Volume 482(2020)
• Page Start: 8
• Page End: 18
• Publication Date: 2020-07-10
• Subjects: SYNPO2 -- CaN -- Cytoplasmic redistribution -- HCC -- Prognostic marker; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.04.005
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Hepatocellular carcinoma (HCC), a type of malignant liver tumor, has a grim prognosis. As a functional protein, synaptopodin-2 (SYNPO2) has been associated with malignancy; however, the expression profile and function of SYNPO2 in HCC remains unknown. Herein, we revealed that SYNPO2 was transcriptionally downregulated in HCC tissues from both The Cancer Genome Atlas cohort and our cohort, and was also decreased at the translational level as determined by western blotting and immunohistochemical staining. Furthermore, reduced SYNPO2 expression correlated significantly with short overall survival and recurrence free survival of HCC patients. Restoring SYNPO2 expression inhibited the proliferation and aggressiveness of hepatocarcinoma cells. Mechanistically, increasing the ratio of cytoplasmic SYNPO2 to nuclear SYNPO2 was positively associated with recurrence rate in HCC patients; calcineurin (CaN) activity positively correlated with cytoplasmic SYNPO2 levels in HCC tissues; and nuclear-cytoplasmic translocation of SYNPO2 was induced by CaN to facilitate metastasis of HCC through assembly of peripheral actin bundles. In short, our findings uncover a novel role of SYNPO2 in HCC metastasis via the CaN/SYNPO2/F-actin axis, and indicate that SYNPO2 may serve as a possible prognostic marker and novel therapeutic target. Highlights: Reduced SYNPO2 correlates significantly with short overall survival and recurrence free survival of HCC patients. Elevating the ratio of cytoplasmic SYNPO2 to nuclear SYNPO2 induced by CaN increases the recurrence risk for HCC patients. Cytoplasmic SYNPO2 facilitate metastasis of HCC through assembly of peripheral actin bundles. SYNPO2 may be a promising prognostic biomarker and novel therapeutic target for HCC.