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.
基金：
National Key R&D Program of China
(2020YFA0112300), National Science Foundation of China (U2102203 to CC and
82203411 to MH); Yunnan Applied Basic Research Projects (202101AS070050 and
202301AY070001-264); Major projects for fundamental research of Yunnan province
(202201BC070002); China Postdoctoral Science Foundation (2023M731448)；Biomedical Projects of Yunnan Key Science and Technology Program (202302AA310046)；
Scientific Research Fund of Yunnan Provincial Department of Education (2023Y0787);
Expert Workstation of Ceshi Chen in Yunnan (Kunming) (YSZ-JFZZ-2020025); Yunnan
Clinical Medical Center of Organ Transplantation (ZX2019-07-01).
第一作者机构：[1]Chinese Acad Sci, Kunming Inst Zool, Kunming 650201, Peoples R China[2]Kunming Med Univ, Affiliated Calmette Hosp, Peoples Hosp Kunming City 1, Kunming 650224, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Chinese Acad Sci, Kunming Inst Zool, Kunming 650201, Peoples R China[3]Kunming Med Univ, Affiliated Hosp 3, Kunming 650118, Peoples R China[5]Kunming Med Univ, Acad Biomed Engn, Kunming 650500, Peoples R China
推荐引用方式(GB/T 7714)：
Huang Maobo,Liu Wenjing,Cheng Zhuo,et al.Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells[J].CELL DEATH DISCOVERY.2024,10(1):doi:10.1038/s41420-024-02154-5.
APA：
Huang, Maobo,Liu, Wenjing,Cheng, Zhuo,Li, Fubing,Kong, Yanjie...&Chen, Ceshi.(2024).Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells.CELL DEATH DISCOVERY,10,(1)
MLA：
Huang, Maobo,et al."Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells".CELL DEATH DISCOVERY 10..1(2024)
