Laboratory of Immunology, Centre for DNA Fingerprinting & Diagnostics, Hyderabad, India.
Graduate Studies, Manipal Academy of Higher Education, Manipal, India.
FEBS Lett. 2022 Jul;596(14):1765-1777. doi: 10.1002/1873-3468.14372. Epub 2022 May 25.
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.
丝状肌动蛋白结合蛋白调控着肌动蛋白聚合，其平衡表达对细胞生长和发育至关重要。大多数肿瘤中丝状肌动蛋白结合蛋白的表达受到抑制，有报道称，在 MDA-MB-231 乳腺癌细胞中过表达丝状肌动蛋白结合蛋白可激活 AMP 激活的蛋白激酶α（AMPKα），这是一种能量感应分子，可影响包括自噬在内的多种细胞过程。本研究旨在探索丝状肌动蛋白结合蛋白在自噬诱导中的作用。我们采用全反式视黄酸（ATRA）作为丝状肌动蛋白结合蛋白表达的诱导剂，结果表明，丝状肌动蛋白结合蛋白通过抑制 mTOR、上调自噬激活激酶 ULK1 以及稳定和激活 AMPK 诱导自噬。此外，本研究的证据表明丝状肌动蛋白结合蛋白与 AMPK 之间存在物理相互作用，导致 AMPK 稳定和延长自噬的诱导，从而导致细胞凋亡。本研究揭示了一种诱导三阴性乳腺癌细胞自噬的新机制。
