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Molecular Cancer
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Research

Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in gastric cancer

Authors: Qirong Geng, Jianjun Liu, Zhaohui Gong, Shangxiang Chen, Shuai Chen, Xiaoxing Li, Yue Lu, Xiaofeng Zhu, Hui-kuan Lin, Dazhi Xu

Published in: Molecular Cancer | Issue 1/2017

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Abstract

Background

Both mTOR and Skp2 play critical roles in gastric cancer (GC) tumorigenesis. However, potential mechanisms for the association between these two proteins remains unidentified.

Methods

The regulatory role for mTORC1 in Skp2 stability was tested using ubiquitination assay. The functions of p-Skp2 (phosphorylation of Skp2) were studied in vitro and in vivo. Expression of p-Skp2 and p-mTOR (phosphorylation of mTOR) were shown in GC lines and in 169 human primary GC tissues.

Results

mTORC1 can directly interact with Skp2 and phosphorylated Skp2 at Ser64, which sequentially protect Skp2 from ubiquitination and degradation. Furthermore, the phospho-deficient p-Skp2 (S64) mutant significantly suppresses GC cell proliferation and tumorigenesis. The expression of p-Skp2 was associated with p-mTOR in GC cell lines and tissues. Interestingly, the combination of p-Skp2 and p-mTOR was a better predictor of survival than either factor alone.

Conclusion

The mTORC1 function to regulate Skp2 by Ser64 phosphorylation may represent an oncogenic event in GC tumorigenesis. Moreover, our study also indicates that Skp2 Ser64 expression is a potential indicator in the treatment of GC patients using mTORC1 inhibitor.
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Metadata
Title
Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in gastric cancer
Authors
Qirong Geng
Jianjun Liu
Zhaohui Gong
Shangxiang Chen
Shuai Chen
Xiaoxing Li
Yue Lu
Xiaofeng Zhu
Hui-kuan Lin
Dazhi Xu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0649-0

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