Faculty Collaboration Database

Metabolic regulation of invadopodia and invasion by acetyl-CoA carboxylase 1 and de novo lipogenesis. PLoS One 2012;7(1):e29761

Date

01/13/2012

Pubmed ID

22238651

Pubmed Central ID

PMC3253107

DOI

10.1371/journal.pone.0029761

Scopus ID

2-s2.0-84855451705 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

Invadopodia are membrane protrusions that facilitate matrix degradation and cellular invasion. Although lipids have been implicated in several aspects of invadopodia formation, the contributions of de novo fatty acid synthesis and lipogenesis have not been defined. Inhibition of acetyl-CoA carboxylase 1 (ACC1), the committed step of fatty acid synthesis, reduced invadopodia formation in Src-transformed 3T3 (3T3-Src) cells, and also decreased the ability to degrade gelatin. Inhibition of fatty acid synthesis through AMP-activated kinase (AMPK) activation and ACC phosphorylation also decreased invadopodia incidence. The addition of exogenous 16∶0 and 18∶1 fatty acid, products of de novo fatty acid synthesis, restored invadopodia and gelatin degradation to cells with decreased ACC1 activity. Pharmacological inhibition of ACC also altered the phospholipid profile of 3T3-Src cells, with the majority of changes occurring in the phosphatidylcholine (PC) species. Exogenous supplementation with the most abundant PC species, 34∶1 PC, restored invadopodia incidence, the ability to degrade gelatin and the ability to invade through matrigel to cells deficient in ACC1 activity. On the other hand, 30∶0 PC did not restore invadopodia and 36∶2 PC only restored invadopodia incidence and gelatin degradation, but not cellular invasion through matrigel. Pharmacological inhibition of ACC also reduced the ability of MDA-MB-231 breast, Snb19 glioblastoma, and PC-3 prostate cancer cells to invade through matrigel. Invasion of PC-3 cells through matrigel was also restored by 34∶1 PC supplementation. Collectively, the data elucidate the novel metabolic regulation of invadopodia and the invasive process by de novo fatty acid synthesis and lipogenesis.

Author List

Scott KE, Wheeler FB, Davis AL, Thomas MJ, Ntambi JM, Seals DF, Kridel SJ

Author

Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3T3 Cells
Acetyl-CoA Carboxylase
Animals
Cell Adhesion
Cell Movement
Cell Surface Extensions
Gene Expression Regulation, Neoplastic
Genes, src
Humans
Lipogenesis
Male
Mice
Neoplasm Invasiveness
Neoplasms
RNA, Small Interfering
Tumor Cells, Cultured