The Role of Inflammatory Response Element CTBP1 in Metabolic Syndrome and Prostate Cancer Metastasis
Introduction: Prostate Cancer (PCa) has a higher prevalence of metastasis in obese patients, which is thought to be a result of increased inflammation causes by obesity and metabolic syndrome, particularly a higher prevalence of visceral fat.1 When immunodeficient mice were used as a model for prostate tumor progression, high fat diet (HFD) was not shown to be a causative factor for enhanced tumor growth.2 This indicates that the mechanism of how HFD increases the severity and enhances progression of prostate cancer is likely to involve inflammatory factors within the immune system, one of which being C-terminal binding protein 1 (CTBP1).2 Methods: Mice xenograft tumor model experiments were run in both CTBP1 depleted and CTBP1 overexpressed models along with different groups among these models of high fat diet and control fed diet mice. Cell lines PC3, 22Rv1, DU145, LNCaP, and C4-2 were used.1,2,3 Results: Results revealed that CTBP1 overexpression decreased adhesion of PCa cells, while also impacting cell morphology, including increasing the prevalence of filopodia. CTBP1 overexpression conferred epithelial to mesenchymal transition (EMT): significant repression of CDH1, an epithelial marker, and significantly induced VIM, a mesenchymal marker.2 When CTBP1 levels were diminished, miRNA expression was found to be downregulated in miRNAs associated with cell adhesion, hsa-miR-19b-3p and hsa-miR-454-30, while the tumor suppressor miRNA, hsa-miR-205-5p, was upregulated when CTBP1 was depleted.2 MiR-196b-5p, a miRNA which targets an EMT inhibitor, CLCA2, was upregulated when CTBP1 levels were elevated.3 Conclusion: CTBP1 has been shown to promote metastasis of prostate cancer in the presence of metabolic syndrome by diminishing adhesion, changing cell morphology, and with regulation of miRNAs promoting cell adhesion and tumor suppression.2 These findings could potentially elucidate possible treatment options by targeting CTBP1 and biomarkers for prostate cancer using the oncomiR miRNA cluster associated with CTBP1 expression.3
- Massillo C, Dalton GN, Porretti J, et al. CTBP1/CYP19A1/estradiol axis together with adipose tissue impacts over prostate cancer growth associated to metabolic syndrome. International Journal of Cancer. 2018;144(5):1115-1127. doi:10.1002/ijc.31773.
- Dalton GN, Massilo C, Scalise GD. CTBP1 depletion on prostate tumors deregulates miRNA/mRNA expression and impairs cancer progression in metabolic syndrome mice. Cell Death and Disease. April 2019.
- Porretti J, Dalton GN, Massillo C, et al. CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR-196b-5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease. International Journal of Cancer. 2018;143(4):897-906. doi:10.1002/ijc.31379