1. Academic Validation
  2. Ambra1 regulates apoptosis and chemosensitivity in breast cancer cells through the Akt-FoxO1-Bim pathway

Ambra1 regulates apoptosis and chemosensitivity in breast cancer cells through the Akt-FoxO1-Bim pathway

  • Apoptosis. 2022 Jun;27(5-6):329-341. doi: 10.1007/s10495-022-01718-z.
Wei-Liang Sun  # 1 Ling-Yan He  # 2 Li Liang 2 Si-Yu Liu 2 Jie Luo 2 Mei-Ling Lv 2 Zheng-Wen Cai 2
Affiliations

Affiliations

  • 1 Department of Medical Oncology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxuedonglu Road, Nanning, 530007, Guangxi, People's Republic of China. sunweiliang@stu.gxmu.edu.cn.
  • 2 Department of Medical Oncology, the Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxuedonglu Road, Nanning, 530007, Guangxi, People's Republic of China.
  • # Contributed equally.
Abstract

The sensitivity of cells to chemotherapeutic agents has a major effect on disease outcome in breast Cancer patients. Unfortunately, there are numerous factors involved in the regulation of chemosensitivity, and the mechanisms need to be further investigated. Autophagy/Beclin 1 regulator 1 (Ambra1) is a key protein in the crosstalk between Autophagy and Apoptosis. It controls the switch between these two processes, which determines whether cells survive or die. Induction of Apoptosis is the primary mechanism by which most chemotherapeutic drugs eliminate Cancer cells. Recently, Ambra1 has been shown to modulate paclitaxel-induced Apoptosis in breast Cancer cells via the Bim/mitochondrial pathway, thereby modifying the sensitivity of cells to paclitaxel. However, how Ambra1 regulates Bim expression remains unclear. Here, we further confirmed that Bim plays an indispensable role in Ambra1's regulation of Apoptosis and chemosensitivity in breast Cancer cells. Furthermore, Ambra1 was found to regulate Bim expression at the transcriptional level through the Akt-FoxO1 pathway. Therefore, we propose a novel pathway, Ambra1-Akt-FoxO1-Bim, which regulates Apoptosis and chemosensitivity in breast Cancer cells. Thus, Ambra1 may represent a potential target for breast Cancer treatment.

Keywords

Ambra1; Apoptosis; Bim; Breast cancer; Chemotherapy; FoxO1.

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