Cip2a induces arginine biosynthesis and promotes tumor progression in non-small cell lung cancer
Danyang Chen
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorSiwen Fan
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorJun Wang
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorYanqing Liang
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorPan Li
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorXinwu Lv
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorYanqin Sun
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorQian Wang
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorHao Liu
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorCorresponding Author
Chuantao Zhang
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Correspondence Yanmei Yi, School of Basic Medical Sciences, Guangdong Medical University, No.2 Wenmingdong Rd, Zhanjiang, Guangdong 524023, China.
Email: [email protected]
Chuantao Zhang, Department of Oncology, Affiliated Hospital of Qingdao University, No. 7 Jiaxing Rd, Qingdao, Shandong 266003, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yanmei Yi
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Correspondence Yanmei Yi, School of Basic Medical Sciences, Guangdong Medical University, No.2 Wenmingdong Rd, Zhanjiang, Guangdong 524023, China.
Email: [email protected]
Chuantao Zhang, Department of Oncology, Affiliated Hospital of Qingdao University, No. 7 Jiaxing Rd, Qingdao, Shandong 266003, China.
Email: [email protected]
Search for more papers by this authorDanyang Chen
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorSiwen Fan
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorJun Wang
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorYanqing Liang
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorPan Li
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorXinwu Lv
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorYanqin Sun
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Search for more papers by this authorQian Wang
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorHao Liu
Guangzhou Key Laboratory of “Translational Medicine on Malignant Tumor Treatment”, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China
Search for more papers by this authorCorresponding Author
Chuantao Zhang
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Correspondence Yanmei Yi, School of Basic Medical Sciences, Guangdong Medical University, No.2 Wenmingdong Rd, Zhanjiang, Guangdong 524023, China.
Email: [email protected]
Chuantao Zhang, Department of Oncology, Affiliated Hospital of Qingdao University, No. 7 Jiaxing Rd, Qingdao, Shandong 266003, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yanmei Yi
School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China
Correspondence Yanmei Yi, School of Basic Medical Sciences, Guangdong Medical University, No.2 Wenmingdong Rd, Zhanjiang, Guangdong 524023, China.
Email: [email protected]
Chuantao Zhang, Department of Oncology, Affiliated Hospital of Qingdao University, No. 7 Jiaxing Rd, Qingdao, Shandong 266003, China.
Email: [email protected]
Search for more papers by this authorDanyang Chen, Siwen Fan, and Jun Wang authors contributed equally to this study.
Abstract
Cancerous inhibitor of protein phosphatase 2A (Cip2a) is an oncoprotein, playing important roles in tumor progression. However, the underlying mechanisms by which Cip2a promotes tumor aggressiveness in NSCLC remain to be further investigated. In this study, we found that Cip2a expression is elevated in NSCLC and correlates with poor prognosis. Knockdown of Cip2a significantly reduced the ability of cell proliferation, invasion, and metastasis of NSCLC both in vitro and in vivo. Furthermore, we found that Cip2a promotes tumor progression partly by inducing arginine biosynthesis, and knockdown of Cip2a exhibited a significantly increased sensitivity to arginine deprivation and mTOR inhibition. In addition, we found that p53 mutants in NSCLC cells increased Cip2a expression by inhibiting the activity of wild-type p53. Our findings provide new insights into the mechanisms of Cip2a in promoting tumor progression and suggest that Cip2a represents a potential therapeutic target for treating NSCLC.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
All data in our study are available upon request.
Supporting Information
| Filename | Description |
|---|---|
| mc23507-sup-0001-Supplementary_Figures-revised.docx1.2 MB | Supporting information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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