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Synaptopodin-2 promotes hepatocellular carcinoma metastasis via calcineurin-induced nuclear-cytoplasmic translocation.
- Source :
-
Cancer letters [Cancer Lett] 2020 Jul 10; Vol. 482, pp. 8-18. Date of Electronic Publication: 2020 Apr 09. - Publication Year :
- 2020
-
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.<br />Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Cell Line, Tumor
Cell Movement
Cell Nucleus metabolism
Cell Proliferation
Cytoplasm metabolism
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Liver Neoplasms genetics
Liver Neoplasms metabolism
Male
Mice
Neoplasm Metastasis
Neoplasm Transplantation
Prognosis
Protein Transport
Survival Analysis
Calcineurin metabolism
Carcinoma, Hepatocellular pathology
Liver Neoplasms pathology
Microfilament Proteins genetics
Microfilament Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 482
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 32278815
- Full Text :
- https://doi.org/10.1016/j.canlet.2020.04.005