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.
摘要：
蛋白磷酸酶2A（Cip2a）的癌性抑制剂是一种癌蛋白，在肿瘤进展中发挥重要作用。然而,Cip2a促进NSCLC肿瘤侵袭性的潜在机制仍有待进一步研究。在这项研究中,我们发现Cip2a在非小细胞肺癌中表达升高,并与不良预后相关.敲除Cip2a显著降低细胞增殖能力,入侵,和NSCLC的体内外转移。此外，我们发现Cip2a部分通过诱导精氨酸生物合成促进肿瘤进展，Cip2a的敲除对精氨酸剥夺和mTOR抑制的敏感性显着增加。此外,我们发现NSCLC细胞中的p53突变体通过抑制野生型p53的活性而增加Cip2a的表达。我们的发现为Cip2a促进肿瘤进展的机制提供了新的见解，并表明Cip2a代表了治疗NSCLC的潜在治疗靶标。
