2. Academic Validation
  3. TNFAIP2 promotes HIF1α transcription and breast cancer angiogenesis by activating the Rac1-ERK-AP1 signaling axis

TNFAIP2 promotes HIF1α transcription and breast cancer angiogenesis by activating the Rac1-ERK-AP1 signaling axis

  • Cell Death Dis. 2024 Nov 13;15(11):821. doi: 10.1038/s41419-024-07223-2.
Wenlong Ren # 1 2,  Huichun Liang # 2,  Jian Sun 3,  Zhuo Cheng 2,  Wenjing Liu 3,  Yingying Wu 4,  Yujie Shi 5,  Zhongmei Zhou 6,  Ceshi Chen 7 8 9
Affiliations

Affiliations

  • 1 School of Life Science, University of Science & Technology of China, Hefei, Anhui, China.
  • 2 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
  • 3 Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China.
  • 4 Department of Pathology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • 5 Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan, China. shiyujie523@126.com.
  • 6 The School of Continuing Education, Kunming Medical University, Kunming, China. zhouzhongmei@kmmu.edu.cn.
  • 7 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. chenc@kmmu.edu.cn.
  • 8 Yunnan Key Laboratory of Breast Cancer Precision Medicine, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Peking University Cancer Hospital Yunnan, Kunming, China. chenc@kmmu.edu.cn.
  • 9 Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical University, Kunming, ChinaAcademy of Biomedical Engineering, Kunming Medical University, Kunming, China. chenc@kmmu.edu.cn.
  • # Contributed equally.
PMID: 39532855 DOI: 10.1038/s41419-024-07223-2
Abstract

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-HIF1α 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 HIF1α 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.

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