2. Academic Validation
  3. GLUT1 participates in tamoxifen resistance in breast cancer cells through autophagy regulation

GLUT1 participates in tamoxifen resistance in breast cancer cells through autophagy regulation

  • Naunyn Schmiedebergs Arch Pharmacol. 2021 Jan;394(1):205-216. doi: 10.1007/s00210-020-01893-3.
Mengqi Sun 1,  Shu Zhao 1,  Yuchen Duan 2,  Yumeng Ma 3,  Yicheng Wang 4,  Hongfei Ji 5,  Qingyuan Zhang 6
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150081, People's Republic of China.
  • 2 Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People's Republic of China.
  • 3 Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, 157 Baojian Road, Harbin, Heilongjiang, 150081, People's Republic of China.
  • 4 College of Bioinformatics Science and Technology, Harbin Medical University, 157 Baojian Road, Harbin, Heilongjiang, 150081, People's Republic of China.
  • 5 Heilongjiang Cancer Research and Prevention Institute, 150 Haping Road, Harbin, Heilongjiang, 150081, People's Republic of China.
  • 6 Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150081, People's Republic of China. zhangqingyuan@hrbmu.edu.cn.
PMID: 32500187 DOI: 10.1007/s00210-020-01893-3
Abstract

Tamoxifen is an estrogen modulator widely used in the treatment of patients with ESR/ER-positive breast cancer; however, resistance limits its clinical application. Autophagy alterations have recently been suggested as a new mechanism for tamoxifen resistance. Glucose transporter 1 (GLUT1) has been reported to be associated with the development and metastasis of breast Cancer, but the relationship among GLUT1, Autophagy, and endocrine resistance remains unclear. Our present study found that GLUT1 expression and Autophagy flux were upregulated in the tamoxifen-resistant breast Cancer cell line MCF-7/TAMR-1 and that knockdown of GLUT1 promoted sensitization to tamoxifen. Moreover, knockdown of GLUT1 significantly decreased the enhancement of Autophagy flux in tamoxifen-resistant cell lines. Furthermore, inhibiting Autophagy in tamoxifen-resistant cells resulted in sensitization to tamoxifen. We conclude that GLUT1 contributes to tamoxifen resistance in breast Cancer and that tamoxifen-resistant cells become resensitized to tamoxifen after GLUT1 silencing. These findings suggest GLUT1 as a new factor clinically associated with resistance to tamoxifen.

Keywords

Autophagy; Breast cancer; GLUT1; Tamoxifen resistance.

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