Profilin upregulation induces autophagy through stabilization of AMP‐activated protein kinase

Profilin regulates actin polymerization, and its balanced expression is required for cellular growth and development. Most tumours have compromised profilin expression, and its overexpression in MDA MB‐231 breast cancer cells has been reported to activate AMP‐activated protein kinase α (AMPKα), an energy‐sensing molecule that affects various cellular processes including autophagy. This study aims to explore the role of profilin in autophagy induction. We employed all‐trans retinoic acid (ATRA) as an inducer of profilin expression and showed that profilin induces autophagy through mTOR inhibition, autophagy‐activating kinase ULK1 upregulation, and AMPK stabilization as well as its activation. Furthermore, evidence from our study indicates physical interaction between profilin and AMPK, which results in AMPK stabilization and induction of prolonged autophagy, thereby leading to apoptosis. This study uncovers a novel mechanism that induces autophagy in triple‐negative breast cancer cells. All‐trans retinoic acid (ATRA) induces expression of profilin, a cytoskeletal regulatory protein which interacts with AMP‐activated protein kinase α (AMPKα), an energy‐sensing molecule. This interaction leads to stabilization and activation of AMPK, which induces autophagy through mTOR inhibition and autophagy‐activating kinase ULK1 upregulation, and results in prolonged autophagy. This study uncovers a novel role of profilin involving AMPK to induce autophagy in triple‐negative breast cancer cells.