Lin Lin, Li Ming, Lin Lei, Xu Xiaolin, Jiang Gening, Wu Liang
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Tongji University School of Medicine, Shanghai 200092, China.
Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University, Shanghai 200072, China.
Biochem Biophys Res Commun. 2018 Feb 5;496(2):536-541. doi: 10.1016/j.bbrc.2018.01.066. Epub 2018 Jan 11.
Farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, was recently shown to play a role in cancer progression. However, its role in non-small cell lung cancer (NSCLC) metastasis and the underlying mechanism remain unclear. In this study, FPPS expression was significantly correlated with TNM stage, and metastasis. Inhibition or knockdown of FPPS blocked TGF-β1-induced cell invasion and epithelial-to-mesenchymal transition (EMT) process. FPPS expression of FPPS was induced by TGF-β1 and FPPS promoted cell invasion and EMT via the RhoA/Rock1 pathway. In conclusion, FPPS mediates TGF-β1-induced lung cancer cell invasion and EMT via the RhoA/Rock1 pathway. These findings suggest new treatment strategies to reduce mortality associated with metastasis in patients with NSCLC.
法尼基焦磷酸合酶（FPPS）是甲羟戊酸途径中的关键酶，最近研究表明其在癌症进展中发挥作用。然而，其在非小细胞肺癌（NSCLC）转移中的作用及潜在机制仍不清楚。在本研究中，FPPS表达与TNM分期及转移显著相关。抑制或敲低FPPS可阻断TGF-β1诱导的细胞侵袭和上皮-间质转化（EMT）过程。TGF-β1可诱导FPPS表达，且FPPS通过RhoA/Rock1途径促进细胞侵袭和EMT。总之，FPPS通过RhoA/Rock1途径介导TGF-β1诱导的肺癌细胞侵袭和EMT。这些发现提示了降低NSCLC患者转移相关死亡率的新治疗策略。
