PCYT1A suppresses proliferation and migration via inhibiting mTORC1 pathway in lung adenocarcinoma
PCYT1A suppresses proliferation and migration via inhibiting mTORC1 pathway in lung adenocarcinoma
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PCYT1A通过抑制mTORC1通路抑制肺腺癌的增殖和迁移
DOI：
10.1016/j.bbrc.2020.05.164
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发表时间：
2020
影响因子：
3.1
通讯作者：
Jin Guoxiang
中科院分区：
文献类型：
--
作者：
Yu Jing;Wu Changtao;Wu Qi;Huang Jiafeng;Fu Wenjuan;Xie Xuemei;Li Wen;Tang Weizhong;Xu Chuan;Jin Guoxiang
肺癌是世界范围内最常见的恶性肿瘤之一。PCYT1A是磷脂酰胆碱生物合成所需的限速酶，与癌症进展相关。然而，PCYT1A在肺腺癌中的生物学功能和潜在的分子机制仍不清楚。在这里，我们发现PCYT1A抑制肺腺癌癌细胞的增殖和迁移。从机制上讲，PCYT1A是mTORC 1信号转导的一种新型负调节因子。PCYT1A基因敲低通过激活mTORC 1增强肺腺癌细胞的恶性增殖和迁移。当mTORC 1信号被雷帕霉素或RAPTOR耗竭抑制时，PCYT1A沉默对细胞增殖和迁移的促进作用可以被消除。重要的是，PCYT1A高表达预测肺癌患者的生存期更长。PCYT1A的表达与mTORC1的激活呈负相关。因此，我们揭示了PCYT1A通过抑制mTORC 1信号通路抑制肺腺癌的增殖和迁移。PCYT1A在肺腺癌中显示出潜在的生物学标记物。
Lung cancer is one of most common malignant cancer worldwide. It is emerging that PCYT1A, a rate-limiting enzyme required for the biosynthesis of phosphatidylcholine, is associated with cancer progression. However, the biological functions and underlying molecular mechanisms of PCYT1A in lung adenocarcinoma is still unknown. Here we found that PCYT1A suppressed lung adenocarcinoma cancer cell proliferation and migration. Mechanically, PCYT1A served as a novel negative regulator of mTORC1 signaling. PCYT1A knockdown enhanced the malignant proliferation and migration of lung adenocarcinoma cells by activating mTORC1. The promoting effects of PCYT1A silencing on cell proliferation and migration could be abolished when mTORC1 signaling was inhibited by rapamycin or RAPTOR depletion. Importantly, PCYT1A high expression predicted longer survival of lung cancer patients. The expression of PCYT1A was also negatively correlated with mTORC1 activation in the clinical lung cancer samples. We therefore reveal that PCYT1A suppresses proliferation and migration by inhibiting the mTORC1 signaling pathway in lung adenocarcinoma. PCYT1A shows as a potential promising biomarker in lung adenocarcinoma.