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Reduced expression of SOX7 in ovarian cancer: a novel tumor suppressor through the Wnt/?-catenin signaling pathway.

ABSTRACT: BACKGROUND: Products of the SOX gene family play important roles in the life process. One of the members, SOX7, is associated with the development of a variety of cancers as a tumor suppression factor, but its relevance with ovarian cancer was unclear. In this study, we investigated the involvement of SOX7 in the progression and prognosis of epithelial ovarian cancer (EOC) and the involved mechanisms. METHODS: Expression profiles in two independent microarray data sets were analyzed for SOX7 between malignant and normal tissues. The expression levels of SOX7 in EOC, borderline ovarian tumors and normal ovarian tissues were measured by immunohistochemistry. We also measured levels of COX2 and cyclin-D1 to examine their possible involvement in the same signal transduction pathway as SOX7. RESULTS: The expression of SOX7 was significantly reduced in ovarian cancer tissues compared with normal controls, strongly indicating that SOX7 might be a negative regulator in the Wnt/?-catenin pathway in ovarian cancer. By immunohistochemistry staining, the protein expression of SOX7 showed a consistent trend with that of the gene expression microarray analysis. By contrast, the protein expression level of COX2 and cyclin-D1 increased as the tumor malignancy progressed, suggesting that SOX7 may function through the Wnt/?-catenin signaling pathway as a tumor suppressor. In comparison between the protein expression levels of SOX7 with pathological features of the cancer, we found that SOX7 was down-regulated mainly in serous cystadenocarcinoma and advanced stages of the cancers. CONCLUSIONS: The expression of SOX7 correlates with tumor progression as a tumor suppressor, possibly through the Wnt/?-catenin signaling pathway in ovarian cancers, suggesting that SOX7 may be a promising prognostic marker.

SUBMITTER: Liu H

PROVIDER: S-EPMC4172779 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Reduced expression of SOX7 in ovarian cancer: a novel tumor suppressor through the Wnt/β-catenin signaling pathway.

Liu Huidi H Yan Zi-Qiao ZQ Li Bailiang B Yin Si-Yuan SY Sun Qiang Q Kou Jun-Jie JJ Ye Dan D Ferns Kelsey K Liu Hong-Yu HY Liu Shu-Lin SL

Journal of ovarian research 20140905

<h4>Background</h4>Products of the SOX gene family play important roles in the life process. One of the members, SOX7, is associated with the development of a variety of cancers as a tumor suppression factor, but its relevance with ovarian cancer was unclear. In this study, we investigated the involvement of SOX7 in the progression and prognosis of epithelial ovarian cancer (EOC) and the involved mechanisms.<h4>Methods</h4>Expression profiles in two independent microarray data sets were analyzed ...[more]

PMID: 25297608

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Project description:BackgroundOvarian cancer is the most lethal gynecologic malignancy worldwide. Olaparib, an inhibitor of poly (ADP-ribose) polymerase (PARP), is becoming widely used in ovarian cancer treatment. The overall survival of ovarian cancer has not been significantly changed over the past decades and ovarian cancer has become increasingly resistant to the Olaparib. Ubiquitin-conjugating enzyme E2S (UBE2S) has been proved to promote malignant behaviors in many cancers. However, the function of UBE2S in the development and Olaparib resistance of ovarian cancer are unclear.Materials and methodsIn this study, we detected the expression of UBE2S in normal fallopian tube (FT) and HGSOC tissues. A2780 and SKOV3 cells were stably transfected with PCMV-UBE2S, PCMV-UBE2S-C95S, UBE2S shRNAs, and negative controls. The CCK8 assay and clonogenic assay were conducted to analyze ovarian cancer proliferation and Olaparib resistance. The transwell assay was performed to determine the migration and invasion of ovarian cancer cells. The relative protein levels of the Wnt/β-catenin signaling pathway were tested using western blot. The ovarian cancer cells were treated with XAV-939 to investigate the role of Wnt/β-catenin signaling pathway in Olaparib resistance. Moreover, we repeated some above procedures in the xenograft model.ResultsThe results demonstrated that UBE2S was highly upregulated in HGSOC and that high UBE2S expression was correlated with poor outcomes in HGSOC. UBE2S promoted ovarian cancer proliferation and drived the migration and invasion of ovarian cancer cells. UBE2S activated the Wnt/β-catenin signaling pathway in ovarian cancer resulting in Olaparib resistance in vitro and in vivo. Furthermore, UBE2S enhanced the proliferation and Olaparib resistance of ovarian cancer in its enzymatic activity dependent manner.ConclusionsThese data suggest a possible molecular mechanism of proliferation and metastasis of ovarian cancer and highlight the potential role of UBE2S as a therapeutic target in ovarian cancer.

Dataset Information

Reduced expression of SOX7 in ovarian cancer: a novel tumor suppressor through the Wnt/?-catenin signaling pathway.

Publications

Reduced expression of SOX7 in ovarian cancer: a novel tumor suppressor through the Wnt/β-catenin signaling pathway.

Similar Datasets

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