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ATPR-induced G0 /G1 phase arrest in gastric cancer cells by regulating the binding of 14-3-3? and filamin A.

ABSTRACT: 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was able to induce the G0 /G1 phase arrest in gastric cancer SGC-7901 cells by downregulating 14-3-3?. However, the mechanisms underlying this effect have not been fully elucidated. Because 14-3-3? functions as a molecular chaperone on cell cycle regulation, the interaction between 14-3-3? and the target proteins is worth an in-depth study. In this study, the use of targeting proteomics identified 352 14-3-3?-binding proteins in SGC-7901 cells. Analysis of gene ontology (GO) was performed using PANTHER to annotate the biological processes, protein classes, and pathways of these proteins. In 25 cell cycle-related proteins, filamin A was reduced following ATPR treatment, and this change was validated by immunoprecipitation. The cell cycle was arrested at the G0 /G1 phase following ATPR treatment or filamin A silencing in SGC-7901 cells. Furthermore, subcellular expression analysis showed that 14-3-3? and filamin A were transferred from the cytoplasm to the nucleus after ATPR treatment. On the other hand, overexpression of 14-3-3?, in SGC-7901 cells, resulted in an increase in the total cellular level of filamin A and an increase in the subcellular localization of filamin A in the cytoplasm. ATPR treatment of the 14-3-3? overexpression cells decreased the total level of filamin A and redistributed filamin A protein from the cytoplasm to the nucleus. Immunohistochemical analysis showed that the expression levels of 14-3-3? and filamin A in gastric cancer tissues were significantly higher, with a predominant localization in the cytoplasm, compared to the levels in matched tissues. Taken together, our results suggest that ATPR can induce nuclear localization of filamin A by reducing the binding of 14-3-3? and filamin A, which may be the mechanism of ATPR-induced G0 /G1 phase arrest.

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC6051145 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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ATPR-induced G<sub>0</sub> /G<sub>1</sub> phase arrest in gastric cancer cells by regulating the binding of 14-3-3ε and filamin A.

Zhao Yingli Y   Fang Xing X   Fang Hui H   Feng Yubin Y   Chen Feihu F   Xia Quan Q  

Cancer medicine 20180604 7

4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was able to induce the G<sub>0</sub> /G<sub>1</sub> phase arrest in gastric cancer SGC-7901 cells by downregulating 14-3-3ε. However, the mechanisms underlying this effect have not been fully elucidated. Because 14-3-3ε functions as a molecular chaperone on cell cycle regulation, the interaction between 14-3-3ε and the target proteins is worth an in-depth study. In this study, the use of targeting proteomics identified 352 14-3-3ε-binding proteins  ...[more]

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