CTGF regulates cell proliferation, migration, and glucose metabolism through activation of FAK signaling in triple-negative breast cancer

Connective tissue growth factor (CTGF), also known as CCN2, is a member of the CCN protein family of secreted proteins with roles in diverse biological processes. CTGF regulates biological functions such as cell proliferation, migration, adhesion, wound healing, and angiogenesis. In this study, we demonstrate a mechanistic link between CTGF and enhanced aerobic glycolysis in triple-negative breast cancer (TNBC). We found that CTGF is overexpressed in TNBC and high CTGF expression is correlated with a poor prognosis. Also, CTGF was required for in vivo tumorigenesis and in vitro proliferation, migration, invasion, and adhesion of TNBC cells. Our results indicate that extracellular CTGF binds directly to integrin alpha v beta 3, activating the FAK/Src/NF-kappa B p65 signaling axis, which results in transcriptional upregulation of Glut3. Neutralization of CTGF decreased cell proliferation, migration, and invasion through downregulation of Glut3-mediated glycolytic phenotypes. Overall, our work suggests a novel function for CTGF as a modulator of cancer metabolism, indicating that CTGF is a potential therapeutic target in TNBC.

Automated summary

CTGF is overexpressed in TNBC and associated with poor prognosis. It enhances aerobic glycolysis by activating the FAK/Src/NF-κB p65 signaling axis. The study suggests CTGF as a potential therapeutic target in TNBC.