TitleMitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis.
Publication TypeJournal Article
Year of Publication2022
AuthorsDíaz-Valdivia N, Simón L, Díaz J, Martinez-Meza S, Contreras P, Burgos-Ravanal R, Perez VI, Frei B, Leyton L, Quest AFG
JournalCancers (Basel)
Date Published2022 Jun 10

Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV. These effects correlated with increased reactive oxygen species (ROS) levels that favored CAV1-induced migration and invasion. Interestingly, pY14-CAV1 promoted the metabolic switch associated with increased migration/invasion and augmented ROS-inhibited PTP1B, a phosphatase that controls pY14 levels. Finally, the glycolysis inhibitor 2-deoxy-D-glucose reduced CAV1-enhanced migration in vitro and metastasis in vivo of murine melanoma cells. In conclusion, CAV1 promotes the Warburg effect and ROS production, which inhibits PTP1B to augment CAV1 phosphorylation on tyrosine-14, thereby increasing the metastatic potential of cancer cells.

Alternate JournalCancers (Basel)
PubMed ID35740528
PubMed Central IDPMC9221213
Grant List15130011 / / CONICYT-FONDAP /
1170925 / / FONDECYT /
1210644 / / FONDECYT /
1111 / / ANILLO ACT /
1150744 / / FONDECYT /
1200836 / / FONDECYT /
VIP / / American Federation for Aging Research /
VIP / / Faculty Development Funds from Linus Pauling Institute /
3190330 / / ANID /