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CTBP1 and metabolic syndrome induce an mRNA and miRNA expression profile critical for breast cancer progression and metastasis.

ABSTRACT: Metastatic breast cancer (BrCa) is still one of the main causes of cancer death in women. Metabolic syndrome (MeS), a risk factor for BrCa, is associated to high grade tumors, increased metastasis and recurrence of this disease. C-terminal binding protein 1 (CTBP1) is a co-repressor of tumor suppressor genes that is activated by low NAD⁺/NADH ratio. Previously, we demonstrated that CTBP1 hyperactivation by MeS increased tumor growth in MDA-MB-231-derived xenografts regulating several genes and miRNAs. In this work, our aim was to elucidate the role of CTBP1 and MeS in BrCa metastasis. We found that CTBP1 protein diminished adhesion while increased migration of triple negative BrCa cells. CTBP1 and MeS modulated the expression of multiple genes (ITGB4, ITGB6, PRSS2, COL17A1 and FABP4) and miRNAs (miR-378a-3p, miR-146a-5p, let-7e-3p, miR-381-5p, miR-194-5p, miR-494-3p) involved in BrCa progression of MDA-MB-231-derived xenografts. Furthermore, we demonstrated that MeS increased lung micrometastasis and liver neoplastic disease in mice. CTBP1 hyperactivation seems to be critical for MeS effect on BrCa metastasis since CTBP1 depletion completely impaired the detection of circulating tumor cells. Our results highlight CTBP1 and MeS impact on BrCa progression positioning them as key properties to be considered for BrCa patient prognosis and management.

SUBMITTER: Farre PL

PROVIDER: S-EPMC5862620 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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CTBP1 and metabolic syndrome induce an mRNA and miRNA expression profile critical for breast cancer progression and metastasis.

Farré Paula L PL Scalise Georgina D GD Duca Rocío B RB Dalton Guillermo N GN Massillo Cintia C Porretti Juliana J Graña Karen K Gardner Kevin K De Luca Paola P De Siervi Adriana A

Oncotarget 20180213 17

Metastatic breast cancer (BrCa) is still one of the main causes of cancer death in women. Metabolic syndrome (MeS), a risk factor for BrCa, is associated to high grade tumors, increased metastasis and recurrence of this disease. C-terminal binding protein 1 (CTBP1) is a co-repressor of tumor suppressor genes that is activated by low NAD<sup>+</sup>/NADH ratio. Previously, we demonstrated that CTBP1 hyperactivation by MeS increased tumor growth in MDA-MB-231-derived xenografts regulating several ...[more]

PMID: 29568399

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Project description:Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study's aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (?5 mm), clinical attachment loss (?5 mm), mobility (?0.5 mm), and alveolar bone loss (?40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth ?5 mm (1.37; 1.14 to 1.65), clinical attachment loss ?5 mm (1.19; 1.00 to 1.41), alveolar bone loss ?40% (1.25; 1.00 to 1.56), and tooth mobility ?0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that comprise the metabolic syndrome may play a role in the development or worsening of periodontitis.

Dataset Information

CTBP1 and metabolic syndrome induce an mRNA and miRNA expression profile critical for breast cancer progression and metastasis.

Publications

CTBP1 and metabolic syndrome induce an mRNA and miRNA expression profile critical for breast cancer progression and metastasis.

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