Angiogenesis is well known to play a critical role in breast cancer. We previously reported that TNFAIP2 activates Rac1 to promote triple-negative breast cancer (TNBC) cell proliferation, migration, and chemoresistance. However, the potential contribution of TNFAIP2 to tumor angiogenesis remains unknown. In this study, we demonstrated that TNFAIP2 promotes TNBC angiogenesis by activating the Rac1-ERK-AP1-HIF1 alpha signaling axis. Under hypoxia, TNFAIP2 activates Rac1 and ERK sequentially. Following that, ERK activates the AP-1 (c-Jun/Fra1) transcription factor. By employing chromatin immunoprecipitation and luciferase reporter assays, we showed that AP-1 directly interacts with the HIF1 alpha gene promoter, thereby enhancing its transcription. The combined application of ERK inhibitors, U0126 or trametinib, with the VEGFR inhibitor Apatinib, additively suppresses angiogenesis and tumor growth of HCC1806 in nude mice. These findings provide new therapeutic strategies for TNBC.
基金：
National Natural Science Foundation of China (National Science Foundation of China) [2020YFA0112300, 2023YFA1800500]; National Key R&D Program of China [82060548, U2102203, 82203413]; National Science Foundation of China [202302AA310046]; Biomedical Projects of Yunnan Key Science and Technology Program [202101AY070001-083]; Yunnan Provincial Department of Science and Technology [202201AT070290]; Yunnan Fundamental Research Projects [AMHD-2024-1]; Open Program of Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms; Yunnan Revitalization Talent Support Program (Yunling Scholar Project) [2023M731448]; China Postdoctoral Science Foundation [YSZJGZZ-2020025]; Academician Expert Workstation
第一作者机构：[1]Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China[2]Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models Human Dis Mech, Kunming, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[2]Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models Human Dis Mech, Kunming, Peoples R China[3]Kunming Med Univ, Peking Univ, Yunnan Canc Hosp, Yunnan Key Lab Breast Canc Precis Med,Affiliated, Kunming, Peoples R China[7]Kunming Med Univ, China Acad Biomed Engn, Acad Biomed Engn, Yunnan Key Lab Breast Canc Precis Med, Kunming, Peoples R China
推荐引用方式(GB/T 7714)：
Ren Wenlong,Liang Huichun,Sun Jian,et al.TNFAIP2 promotes HIF1α transcription and breast cancer angiogenesis by activating the Rac1-ERK-AP1 signaling axis[J].CELL DEATH & DISEASE.2024,15(11):doi:10.1038/s41419-024-07223-2.
APA：
Ren, Wenlong,Liang, Huichun,Sun, Jian,Cheng, Zhuo,Liu, Wenjing...&Chen, Ceshi.(2024).TNFAIP2 promotes HIF1α transcription and breast cancer angiogenesis by activating the Rac1-ERK-AP1 signaling axis.CELL DEATH & DISEASE,15,(11)
MLA：
Ren, Wenlong,et al."TNFAIP2 promotes HIF1α transcription and breast cancer angiogenesis by activating the Rac1-ERK-AP1 signaling axis".CELL DEATH & DISEASE 15..11(2024)
生物学