Ambra1 Deficiency Inhibits the Proliferation of Breast Cancer Cells Through the Akt-FoxO1-p27 Pathway.

PURPOSE: The unlimited proliferation of breast cancer (BC) cells is the basis for recurrence and metastasis. Ambra1 is involved in the regulation of cell proliferation, but its role may be cancer type-dependent, and the underlying mechanisms need further exploration. In addition, it remains unclear whether Ambra1 is involved in regulating the proliferation of BC cells. This study aims to explore the regulatory effect of Ambra1 on the proliferation of BC cells, as well as the underlying mechanisms. METHODS: The effects of Ambra1 on cell proliferation were detected in MCF-7 and MDA-MB-231 cells using CCK-8, EdU, and colony formation assays. The role of Ambra1 in regulating p27 via the Akt-FoxO1 pathway was determined in MCF-7, MDA-MB-231, and 293T cells through Western blotting, qRT-PCR, and co-immunoprecipitation. Subsequently, the role of p27 in Ambra1-mediated regulation of cell proliferation was validated in cell models and xenograft mouse models. RESULTS: Ambra1 deficiency significantly inhibited the proliferation of BC cells. p27 played a crucial role in this process. Furthermore, Ambra1 regulates the phosphorylation of the Ser256 residue of FoxO1 through Akt, thereby altering the nuclear distribution of FoxO1 and the transcription of p27. CONCLUSION: Ambra1 can control the proliferation of BC cells by regulating the Akt-FoxO1-p27 signaling pathway. Therefore, this protein is a potential therapeutic target for BC.