Dataset Information

SIRT6 Is Involved in the Progression of Ovarian Carcinomas via ?-Catenin-Mediated Epithelial to Mesenchymal Transition.

ABSTRACT: SIRT6 is involved in various cellular signaling pathways including those involved in tumorigenesis in association with ?-catenin. However, the role of SIRT6 in tumorigenesis has been controversially reported and the studies on the role of SIRT6 in ovarian cancers is limited. In this study, we evaluated the expression and roles of SIRT6 in conjunction with the expression of active ?-catenin in 104 human ovarian carcinomas and ovarian cancer cells. In human ovarian carcinomas, the expressions of SIRT6 and active ?-catenin were associated with higher tumor stage, higher histologic grade, and platinum-resistance. Moreover, nuclear expression of SIRT6 (104 ovarian carcinomas; P = 0.010, 63 high-grade serous carcinomas; P = 0.040), and activated ?-catenin (104 ovarian carcinomas; P = 0.013, 63 high-grade serous carcinomas; P = 0.005) were independent indicators of shorter overall survival of ovarian carcinoma patients in multivariate analysis. In OVCAR3 and OVCAR5 ovarian cancer cells, knock-down of SIRT6 significantly inhibited the migration and invasion of cells, but did not inhibit the proliferation of cells. SIRT6-mediated invasiveness of ovarian cancer cells was associated with the expression of epithelial-to-mesenchymal transition-related signaling molecules such as snail, vimentin, N-cadherin, E-cadherin, and activated ?-catenin. Especially, SIRT6-mediated increase of invasiveness and activation of epithelial-to-mesenchymal transition signaling was attenuated by knock-down of ?-catenin. In conclusion, this study suggests that SIRT6-?-catenin signaling is involved in the epithelial-to-mesenchymal transition of ovarian cancer cells, and the expression of SIRT6 and active ?-catenin might be used as indicators of poor prognosis of ovarian carcinoma patients. In addition, our results suggest that SIRT6-?-catenin signaling might be a new therapeutic target of ovarian carcinomas.

SUBMITTER: Bae JS

PROVIDER: S-EPMC6256124 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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SIRT6 Is Involved in the Progression of Ovarian Carcinomas via β-Catenin-Mediated Epithelial to Mesenchymal Transition.

Bae Jun Sang JS Noh Sang Jae SJ Kim Kyoung Min KM Park See-Hyoung SH Hussein Usama Khamis UK Park Ho Sung HS Park Byung-Hyun BH Ha Sang Hoon SH Lee Ho H Chung Myoung Ja MJ Moon Woo Sung WS Cho Dong Hyu DH Jang Kyu Yun KY

Frontiers in oncology 20181120

SIRT6 is involved in various cellular signaling pathways including those involved in tumorigenesis in association with β-catenin. However, the role of SIRT6 in tumorigenesis has been controversially reported and the studies on the role of SIRT6 in ovarian cancers is limited. In this study, we evaluated the expression and roles of SIRT6 in conjunction with the expression of active β-catenin in 104 human ovarian carcinomas and ovarian cancer cells. In human ovarian carcinomas, the expressions of S ...[more]

PMID: 30524965

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Project description:BackgroundSocial isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. In patients with ovarian cancer, social isolation has been found to be related to decreased survival and multiple biomarkers supporting tumor progression. However, to the authors' knowledge, little is known regarding the relationship between social isolation and the molecular characteristics of ovarian tumors. Herein, the authors have used genome-wide transcriptional profiling to quantify associations between social isolation and epithelial-mesenchymal transition (EMT) polarization in ovarian tumors and transcriptome-driven, promoter-based bioinformatics analyses to identify gene regulatory pathways that may potentially underlie these changes.MethodsTumor was sampled during primary surgical resection and immediately frozen in liquid nitrogen. After RNA extraction, microarray analysis of the transcriptome was performed and samples were analyzed to assess associations between EMT-related gene transcripts and social isolation (as indicated by a Social Provisions Scale Attachment subscale score <15). Convergent validation was provided by a promoter-based bioinformatic analysis of transcription factor activity.ResultsPrimary analyses of 99 women demonstrated a lower average expression of gene transcripts previously associated with epithelial differentiation in women with high social isolation (-0.143 ± 0.048 log2 mRNA abundance; P = .004), but no difference in mesenchymal differentiation as a function of social isolation (+0.007 ± 0.0064 log2 mRNA abundance; P = .900). Upregulated activity was shown for 3 of the 4 targeted EMT-related transcription factors, including GATA4 (P = .014); SMAD2, SMAD3, and/or SMAD4 (P < .001); and TWIST1 (P < .001). Analyses of SNAIL2/SLUG activity indicated a directional trend toward increased activity that did not reach statistical significance (P = .123).ConclusionsThe findings of the current study demonstrated differential EMT polarization and EMT-related transcription factor activity according to social isolation, a known socioenvironmental risk factor.Lay summarySocial isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. Herein, the authors examined the relationship between social isolation and the molecular characteristics of ovarian tumors. The authors investigated the epithelial-mesenchymal transition (EMT), a process whereby tumor cells lose epithelial characteristics and become more embryonic (mesenchymal), thereby enhancing invasiveness. Primary analyses demonstrated lower expression of genes previously associated with epithelial differentiation and increased activity of specific EMT-related transcription factors in individuals with high social isolation, indicating increased EMT polarization in these patients. These findings extend the understanding of how socioenvironmental factors may modulate tumor growth.

Dataset Information

SIRT6 Is Involved in the Progression of Ovarian Carcinomas via ?-Catenin-Mediated Epithelial to Mesenchymal Transition.

Publications

SIRT6 Is Involved in the Progression of Ovarian Carcinomas via β-Catenin-Mediated Epithelial to Mesenchymal Transition.

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