2. Academic Validation
  3. ESR1 inhibits ionizing radiation-induced ferroptosis in breast cancer cells via the NEDD4L/CD71 pathway

ESR1 inhibits ionizing radiation-induced ferroptosis in breast cancer cells via the NEDD4L/CD71 pathway

  • Arch Biochem Biophys. 2022 Aug 15;725:109299. doi: 10.1016/j.abb.2022.109299.
Lin Liu 1,  Chen Zhang 1,  Shugen Qu 1,  Rui Liu 2,  Huajian Chen 1,  Zhenzhen Liang 2,  Zhujun Tian 1,  Lan Li 1,  Shumei Ma 3,  Xiaodong Liu 4
Affiliations

Affiliations

  • 1 School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • 2 NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, Jilin, 130021, China.
  • 3 School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Key Laboratory of Watershed Science and Health of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, Zhejiang, 325035, China. Electronic address: shmm2001@126.com.
  • 4 School of Public Health and Management, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Key Laboratory of Watershed Science and Health of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: liuxd2014@126.com.
PMID: 35613689 DOI: 10.1016/j.abb.2022.109299
Abstract

Ferroptosis is the name given to the type of non-apoptotic cell death that is caused by iron accumulation and subsequent lipid peroxidation. However, how ionizing radiation (IR)-induced Ferroptosis is regulated in estrogen receptor-positive (ER+) breast Cancer cells remains unclear. To attempt to resolve this issue, bioinformatics analysis was performed to evaluate the prognostic value of Estrogen Receptor 1 (ESR1) in breast Cancer tissues. A total of four breast Cancer cell lines and an MCF10A non-malignant counterpart were used. Western blotting was used to analyze the levels of protein expression, whereas immunoprecipitation (IP) and ubiquitination experiments were used to test protein binding and ubiquitination levels, respectively. Flow cytometry was subsequently used to analyze cell death and lipid peroxidation levels. The results showed that a high expression level of ESR1 was significantly correlated with poor overall survival in breast Cancer. ESR1 knockdown significantly enhanced IR-induced Ferroptosis and increased the CD71 protein level. The IP results showed that ESR1 enhanced the binding of the E3 ubiquitin Ligase NEDD4L to CD71, promoting the ubiquitination and degradation of CD71, suggesting that CD71 expression was regulated by both ESR1 and NEDD4L. Taken together, the findings in the present study have demonstrated a regulatory relationship between ESR1 and NEDD4L/CD71 in IR-induced Ferroptosis. In addition, the ESR1/NEDD4L/CD71 axis may be a potential target for the radiotherapy of breast Cancer.

Keywords

Breast cancer; Estrogen receptor 1; Ferroptosis; Ionizing radiation; NEDD4L; Transferrin receptor (CD71).

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