Leng Yahui, Luan Zhenzi, Li Zihang, Ma Yongqing, Zhou Yang, Liu Jiaqi, Liu Song, Tian Tian, Feng Wenxiao, Liu Yanni, Shi Qin, Huang Chengyang, Zhao Xuan, Wang Wenlong, Liu Ao, Wang Tianhang, Ren Qiulei, Liu Jiakun, Huang Qian, Zhang Yaling, Yin Bin, Chen Jialin, Yang Liangliang, Zhao Shiyun, Bao Ruoyi, Ji Xingyu, Xu Yuewen, Liu Liaoyuan, Zhou Junsuo, Chen Miao, Ma Wenhui, Shen Li, Zhang Te, Zhao Hongyan
School of Basic Medicine, Hubei University of Medicine, Shiyan, Hubei, China.
Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Clin Transl Oncol. 2025 Mar;27(3):1013-1025. doi: 10.1007/s12094-024-03614-1. Epub 2024 Aug 12.
PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. Whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and the mechanism of PPM1F in ovarian cancer. The expression level and the survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. A tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We tested the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer.
PPM1F已被证明在多种肿瘤进展中发挥多种生物学功能。PPM1F控制ITGB1的T788/T789磷酸化开关并调节整合素活性。然而，PPM1F和ITGB1对卵巢癌（OV）进展的影响仍不清楚。卵巢癌中PPM1F和ITGB1之间是否存在这种调节关系尚未得到研究。因此，本研究的目的是阐明PPM1F在卵巢癌中的功能和机制。通过数据库分析PPM1F的表达水平和生存曲线。采用功能获得和功能缺失方法探讨PPM1F在卵巢癌中的功能。裸鼠肿瘤形成试验表明，敲低PPM1F可抑制肿瘤形成。我们通过免疫共沉淀和蛋白质印迹法检测了PPM1F对卵巢癌细胞中ITGB1去磷酸化的影响。采用功能缺失方法研究ITGB1在卵巢癌中的功能。ITGB1突变体过表达促进卵巢癌进展。挽救试验表明，由于PPM1F使ITGB1野生型去磷酸化，ITGB1野生型对卵巢癌的促进作用减弱。PPM1F和ITGB1在卵巢癌中发挥癌基因功能。PPM1F调节ITGB1的磷酸化，从而影响卵巢癌的发生和发展。
