Oncoprotein HBXIP induces PKM2 via transcription factor E2F1 to promote cell proliferation in ER-positive breast cancer  

作　　者：Bo-wen Liu Tiarvjiao Wang Lei-lei Li Lu Zhang Yun-xia Liu Jin-yan Feng Yue Wu Fei-fei Xu Quan-sheng Zhang Ming-zhu Bao Wei-ying Zhang Li-hong Ye 

机构地区：[1]Department of Biochemistry, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China [2]Department of Cancer Research, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China [3]Department of Organ Transplantation, Key Laboratory of Organ Transplantation of Tianjin, Tianjin First Central Hospital, Tianjin 300071, China

出　　处：《Acta Pharmacologica Sinica》2019年第4期530-538,共9页中国药理学报（英文版）

基　　金：National Basic Research Program of China (973 Program, No. 2015CB553905);National Natural Science Foundation of China (Nos. 81372186 and 31670771);the Fundamental Research Funds for the Central Universities;Project of Prevention and Control of Key Chronic Non Infectious Diseases (No. 2016YFC1303401).

摘　　要：We have reported that hepatitis B X-interacting protein (HBXIP, also termed LAMT0R5) can act as an oncogenic transcriptional co-activator to modulate gene expression, promoting breast cancer development. Pyruvate kinase muscle isozyme M2 (PKM2), encoded by PKM gene, has emerged as a key oncoprotein in breast cancer. Yet, the regulatory mechanism of PKM2 is still unexplored. Here, we report that HBXIP can upregulate PKM2 to accelerate proliferation of estrogen receptor positive (ER+) breast cancer. Immunohistochemistry analysis using breast cancer tissue microarray uncovered a positive association between the expression of HBXIP and PKM2. We also discovered that PKM2 expression was positively related with HBXIP expression in clinical breast cancer patients by real-time PCR assay. Interestingly, in ER+ breast cancer cells, HBXIP was capable of upregulating PKM2 expressi on at mRNA and protei n levels in a dose-depe ndent manner, as well as in creasing the activity of PKM promoter. Mechanistically, HBXIP could stimulate PKM promoter through binding to the -779/-579 promoter region involving co-activation of E2F transcription factor 1 (E2F1). In function, cell viability, EdU, colony formation, and xenograft tumor growth assays showed that HBXIP contributed to accelerating cell proliferation through PKM2 in ER+ breast cancer. Collectively, we conclude that HBXIP in duces PKM2 through tran scripti on factor E2F1 to facilitate ER+ breast cancer cell proliferation. We provide new evidence for the mechanism of transcription regulation of PKM2 in promotion of breast cancer progression.

关 键 词：HBXIP PKM2 E2F1 BREAST cancer proliferation 

分 类 号：R[医药卫生]