Cip2a induces arginine biosynthesis and promotes tumor progression in non-small cell lung cancer

被引：4

作者：

Chen, Danyang ^{[1
]}

Fan, Siwen ^{[2
]}

Wang, Jun ^{[1
]}

Liang, Yanqing ^{[2
]}

Li, Pan ^{[1
,2
]}

Lv, Xinwu ^{[2
]}

Sun, Yanqin ^{[2
]}

Wang, Qian ^{[1
]}

Liu, Hao ^{[1
]}

Zhang, Chuantao ^{[3
,5
]}

Yi, Yanmei ^{[4
]}

机构：

[1] Affiliated Canc Hosp, Guangzhou Key Lab Translat Med Malignant Tumor Tre, Inst Guangzhou Med Univ, Guangzhou, Guangdong, Peoples R China

[2] Guangdong Med Univ, Sch Basic Med Sci, Zhanjiang, Guangdong, Peoples R China

[3] Qingdao Univ, Dept Oncol, Affiliated Hosp, Qingdao, Shandong, Peoples R China

[4] Guangdong Med Univ, Sch Basic Med Sci, 2Wenmingdong Rd, Zhanjiang 524023, Guangdong, Peoples R China

[5] Affiliated Hosp Qingdao Univ, Dept Oncol, Affiliated Hosp, 7 Jiaxing Rd, Qingdao 266003, Shandong, Peoples R China

来源：

MOLECULAR CARCINOGENESIS | 2023年 / 62卷 / 04期

基金：

中国国家自然科学基金;

关键词：

arginine biosynthesis; Cip2a; NSCLC; PROTEIN PHOSPHATASE 2A; ONCOPROTEIN; INHIBITOR;

D O I：

10.1002/mc.23507

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：561 / 572

页数：12

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