title: Caveolin-1-LRP6 signaling module stimulates aerobic glycolysis in prostate cancer.
abstract: Caveolin 1 (Cav-1) is a plasma membrane-associated protein with the capacity to modulate signaling activities in a context-dependent fashion. Interactions between Cav-1 and low-density lipoprotein receptor-related protein 6 (LRP6) were reported to be important for the regulation of Wnt-β-catenin (β-cat) signaling. Cav-1 also interacts with insulin and IGF-I receptors (IGF-IR/IR) and can stimulate IR kinase activities. We found positive correlation between Cav-1 and LRP6 expression in both human primary prostate cancer and metastasis tissues and in PC-3 cells. Cav-1 stimulation of Wnt-β-cat signaling and c-Myc levels was positively associated with LRP6 expression in LNCaP, PC-3, and DU145 prostate cancer cells. Importantly, LRP6 and, to a lesser extent, Cav-1 were found to stimulate aerobic glycolysis. These activities were positively associated with the expression of HK2 and Glut3 and shown to be dependent on Akt signaling by both gene knockdown and chemical inhibition methods. We further showed that Cav-1 and LRP6 exert their effects on Akt and glycolytic activities by stimulating IGF-IR/IR signaling. Overall, our results show that Cav-1 interacts with LRP6 to generate an integrated signaling module that leads to the activation of IGF-IR/IR and results in stimulation of Akt-mTORC1 signaling and aerobic glycolysis in prostate cancer.
authors.affiliation: Department of Genitourinary Medical Oncology-Research, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Salahaldin A
authors.initials: SA
authors.lastname: Tahir
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Alexei
authors.initials: A
authors.lastname: Goltsov
authors.forename: Ki-Duk
authors.initials: KD
authors.lastname: Song
authors.forename: Chengzhen
authors.initials: C
authors.lastname: Ren
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Chang
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Thompson
mesh_terms: D000332:Aerobiosis; D051242:Caveolin 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D006019:Glycolysis; D006801:Humans; D007150:Immunohistochemistry; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D051242:Caveolin 1; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6