2. Academic Validation
  3. MICAL-L2, as an estrogen-responsive gene, is involved in ER-positive breast cancer cell progression and tamoxifen sensitivity via the AKT/mTOR pathway

MICAL-L2, as an estrogen-responsive gene, is involved in ER-positive breast cancer cell progression and tamoxifen sensitivity via the AKT/mTOR pathway

  • Biochem Pharmacol. 2024 May 9:225:116256. doi: 10.1016/j.bcp.2024.116256.
Pushuai Wen 1,  Jing Li 2,  Zihao Wen 3,  Xiaoyan Guo 2,  Guoqun Ma 3,  Shuzhen Hu 3,  Jiamei Xu 3,  Hongli Zhao 3,  Ruixin Li 3,  Ying Liu 4,  Yu Wang 5,  Jing Gao 6
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Jinzhou Medical University, Jinzhou 121001, China; Biological Anthropology Institute, Jinzhou Medical University, Jinzhou 121001, China. Electronic address: wenpushuai_jzmu@jzmu.edu.cn.
  • 2 Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, China.
  • 3 Department of Pathophysiology, Jinzhou Medical University, Jinzhou 121001, China.
  • 4 Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, China. Electronic address: yingliu@jzmu.edu.cn.
  • 5 Liaoning Technology and Engineering Center for Tumor Immunology and Molecular Theranotics, Collaborative Innovation Center for Age-related Disease, Life Science Institute of Jinzhou Medical University, Jinzhou 121001, China. Electronic address: yuwang@ccmu.edu.cn.
  • 6 Department of Ultrasonography, The First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121001, China. Electronic address: gaoj@jzmu.edu.cn.
PMID: 38729448 DOI: 10.1016/j.bcp.2024.116256
Abstract

Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast Cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast Cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast Cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast Cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERβ signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast Cancer tumorigenesis but also influenced the sensitivity of ER-positive breast Cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the Akt/mTOR signaling pathway in ER-positive breast Cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast Cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast Cancer.

Keywords

Breast cancer; Endocrine therapy; Estrogen receptor; MICAL-L2; Tamoxifen.

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