Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul;596(14):1765-1777.
doi: 10.1002/1873-3468.14372. Epub 2022 May 25.

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

Shashank Saurav  1   2 , Sunil Kumar Manna  1
Affiliations
Free article

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

Shashank Saurav et al. FEBS Lett. 2022 Jul.
Free article

Abstract

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.

Keywords: AMP-activated protein kinase; LAMP 2; LC3; autophagy; profilin; retinoic acid.

PubMed Disclaimer

References

    1. Ding Z, Gau D, Deasy B, Wells A, Roy P. Both actin and polyproline interactions of Profilin-1 are required for migration, invasion and capillary morphogenesis of vascular endothelial cells. Exp Cell Res. 2009;315:2963-73.
    1. Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell. 2003;112:453-65.
    1. Ding Z, Lambrechts A, Parepally M, Roy P. Silencing Profilin-1 inhibits endothelial cell proliferation, migration and cord morphogenesis. J Cell Sci. 2006;119:4127-37.
    1. Witke W, Sutherland JD, Sharpe A, Arai M, Kwiatkowski DJ. Profilin I is essential for cell survival and cell division in early mouse development. Proc Natl Acad Sci USA. 2001;98:3832-6.
    1. Witke W. The role of Profilin complexes in cell motility and other cellular processes. Trends Cell Biol. 2004;14:461-9.

Publication types

MeSH terms

Substances

LinkOut - more resources