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Ambra1 modulates the sensitivity of breast cancer cells to epirubicin by regulating autophagy via ATG12.

ABSTRACT: The sensitivity of breast cancer cells to epirubicin (EPI) is closely related to the efficacy of the drug and the prognosis of patients. A growing body of research has suggested that autophagy is involved in the treatment of a variety of cancers, including breast cancer, and modifies the sensitivity of anticancer drugs. However, the mechanism by which autophagy participates in cancer therapy and modulates drug sensitivity has not been fully elucidated. In this study, we showed that the expression of Autophagy/Beclin 1 regulator 1 (Ambra1), a key protein of autophagy, was negatively correlated with EPI sensitivity in breast cancer cells. In addition, it altered the sensitivity of breast cancer cells to EPI by regulating EPI-induced autophagy. As a potential mechanism, we demonstrated that autophagy-related protein 12 (ATG12) was a downstream protein that Ambra1-regulated EPI-induced autophagy. Therefore, Ambra1 plays an important role in regulating the sensitivity of breast cancer cells to EPI. And the regulatory effect of Ambra1 on EPI sensitivity is achieved through the regulation of autophagy by targeting ATG12. Overall, we propose a novel mechanism by which autophagy modulates the sensitivity of breast cancer cells to EPI. ATG12 is a novel targeting protein of Ambra1 in regulating EPI-induced autophagy. In addition, the important role of Ambra1 in modulating the sensitivity of breast cancer cells to EPI is confirmed in vivo. This finding indicates that Ambra1 might be a target for developing breast cancer treatments.

SUBMITTER: Sun WL

PROVIDER: S-EPMC6172055 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Ambra1 modulates the sensitivity of breast cancer cells to epirubicin by regulating autophagy via ATG12.

Sun Wei-Liang WL Wang Li L Luo Jie J Zhu Hua-Wei HW Cai Zheng-Wen ZW

Cancer science 20180824 10

The sensitivity of breast cancer cells to epirubicin (EPI) is closely related to the efficacy of the drug and the prognosis of patients. A growing body of research has suggested that autophagy is involved in the treatment of a variety of cancers, including breast cancer, and modifies the sensitivity of anticancer drugs. However, the mechanism by which autophagy participates in cancer therapy and modulates drug sensitivity has not been fully elucidated. In this study, we showed that the expressio ...[more]

PMID: 30027574

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Ambra1 modulates the sensitivity of breast cancer cells to epirubicin by regulating autophagy via ATG12.

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Ambra1 modulates the sensitivity of breast cancer cells to epirubicin by regulating autophagy via ATG12.

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