PCNA‐associated factor P15PAF, targeted by FOXM1, predicts poor prognosis in high‐grade serous ovarian cancer patients. Issue 11 (4th October 2018)

• Record Type: Journal Article
• Authors: Jin, Chengjuan; Liu, Zhaojian; Li, Yingwei; Bu, Hualei; Wang, Yu; Xu, Ying; Qiu, Chunping; Yan, Shi; Yuan, Cunzhong; Li, Rongrong; Diao, Nannan; Zhang, Zhiwei; Wang, Xiangxiang; Liu, Lidong; Kong, Beihua
• Is Part Of: International journal of cancer. Volume 143:Issue 11(2018)
• Page Start: 2973
• Page End: 2984
• Publication Date: 2018-10-04
• Subjects: P15PAF -- FOXM1 -- HGSOC -- PI3K/AKT/mTOR; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31800
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Activation of the FOXM1 signaling pathway and the PI3K/AKT/mTOR signaling pathway is associated with poor prognosis in ovarian cancer. In this study, we demonstrated that P15 PAF (KIAA0101) was significantly upregulated in high‐grade serous ovarian cancer (HGSOC) and that high KIAA0101 expression was associated with poor prognosis. FOXM1 transcriptionally activated KIAA0101 to drive proliferation and metastasis of ovarian cancer cells. KIAA0101 activated the PI3K/AKT/mTOR signaling pathway to inhibit cisplatin‐induced apoptosis and autophagy in ovarian cancer cells resulting in cisplatin resistance. Thus, KIAA0101 was closely related to the FOXM1 and PI3K/AKT/mTOR signaling pathways. Collectively, these findings provide insights into the mechanisms of poor prognosis of ovarian cancer and have implications for the development of both predictive and therapeutic biomarkers for the treatment of ovarian cancer. Abstract : What's new? Ovarian cancer may have a new biomarker, KIAA0101. KIAA0101 is known as an oncogene in many cancers, these authors investigated its clinical significance in ovarian cancer for the first time. High‐grade serous ovarian cancer had higher than normal levels of KIAA0101, they found, and elevated levels correlated with poorer outcomes. Using cell lines engineered to overexpress KIAA0101, they showed that the protein promotes proliferation, migration, and chemoresistance. They also learned that FOXM1 regulates KIAA0101 transcription, and KIAA0101 activates the PI3K/AKT/mTOR pathway, leading to cisplatin resistance.