Figure 2
Stimulation of aerobic glycolysis in the development of CRPC. Cav-1 interacts with growth factor receptors and low density lipoprotein receptor-related protein 6 (LRP6). These activities stimulate PI3K/Akt signaling, leading to increased phosphorylation of Akt (pAKT) and increased expression of glycolytic enzymes, that is, glucose transporter 3 (Glut3) and hexokinase II (HK II), promoting aerobic glycolysis. Induction of aerobic glycolyis may contribute to prostate cancer cell survival, proliferation and drug resistance. Cav-1 is secreted by prostate cancer cells and establishes a positive autocrine and paracrine loop within the tumor microenvironment. Secreted, soluble Cav-1 is taken up by prostate cancer cells and can interact with specific growth factor receptors. Cav-1 is also taken up by endothelial cells, and can stimulate angiogenesis, further supporting tumor growth. ADT leads to de-repression of alternative survival pathways, that is, PI3K/Akt and increases Cav-1 expression. These activities may lead to metabolic reprogramming, and potentially contribute to prostate cancer progression.
