2. Academic Validation
  3. Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells

Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells

  • Cell Death Discov. 2024 Nov 1;10(1):462. doi: 10.1038/s41420-024-02154-5.
Maobo Huang # 1 2,  Wenjing Liu # 3,  Zhuo Cheng 1 4,  Fubing Li 5,  Yanjie Kong 6,  Chuanyu Yang 1,  Yu Tang 3,  Dewei Jiang 1,  Wenhui Li 3,  Yudie Hu 7,  Jinhui Hu 8,  PemaTenzin Puno 9,  Ceshi Chen 10 11 12
Affiliations

Affiliations

  • 1 Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China.
  • 2 The First People's Hospital of Kunming City (The Affiliated Calmette Hospital of Kunming Medical University), Kunming, 650224, China.
  • 3 The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China.
  • 4 Kunming College of Life Sciences, University of the Chinese Academy of Sciences, Kunming, 650204, China.
  • 5 Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China.
  • 6 Biobank, Shenzhen Second People's Hospital/ the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China.
  • 7 The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
  • 8 The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China. 1060851534@qq.com.
  • 9 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China. punopematenzin@mail.kib.ac.cn.
  • 10 Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China. chenc@kmmu.edu.cn.
  • 11 The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China. chenc@kmmu.edu.cn.
  • 12 Academy of Biomedical Engineering, Kunming Medical University, Kunming, 650500, China. chenc@kmmu.edu.cn.
  • # Contributed equally.
PMID: 39487119 DOI: 10.1038/s41420-024-02154-5
Abstract

Triple negative breast Cancer is the most malignant subtype of breast Cancer and current treatment options are limited. Radiotherapy is one of the primary therapeutic options for patients with TNBC. In this study, we discovered that the E3 ubiquitin Ligase, HECTD3, promoted TNBC cell survival after irradiation. HECTD3 collaborated with UbcH5b to promote p62 ubiquitination and Autophagy while HECTD3 deletion led to p62 accumulation in the nucleus in response to irradiation, thus inhibiting RNF168 mediated DNA damage repair. Furthermore, the HECTD3/UbcH5b inhibitor, PC3-15, increased the radiosensitivity of TNBC cells by inhibiting DNA damage repair. Taken together, we conclude that HECTD3 promotes Autophagy and DNA damage repair in response to irradiation in a p62-denpendent manner, and that inhibition of the HECTD3-p62 axis could be a potential therapeutic strategy for patients with TNBC in addition to radiotherapy.

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