Dataset Information

Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.

ABSTRACT: Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-?B activity, TUSC3 expression was found to be reversely correlated with NF-?B activity. TUSC3-silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancer patients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-?B activity and TUSC3 expression may suggest a novel regulation pattern for this molecule.

SUBMITTER: Fan X

PROVIDER: S-EPMC4752499 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.

Fan Xiaoqiang X Zhang Xiu X Shen Jie J Zhao Haibin H Yu Xuetao X Chen Yong'an Y Zhuang Zhuonan Z Deng Xiaolong X Feng Hua H Wang Yunfei Y Peng Long L

PloS one 20160212 2

Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 ex ...[more]

PMID: 26871953

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Project description:Aim:The aim of this study was to explore the expression of peroxiredoxin1 (PRDX1) in epithelial ovarian cancer, analyze the relationship between PRDX1 and clinicopathologic parameters of patients with ovarian cancer, including their prognosis, and describe changes and the mechanisms involved in malignant biologic behavior of ovarian cancer cells when PRDX1 expression is inhibited. Methods:The expression of PRDX1 was detected immunohistochemically in 15 samples of normal ovarian tissue, 21 benign, 11 borderline, and 101 malignant epithelial ovarian tumors. Changes in ovarian cancer cell proliferation, invasion, and metastasis before and after inhibiting PRDX1 expression were assessed by cell function assay. Additionally, gene set enrichment analysis (GSEA) of PRDX1 was performed by the Cancer Genome Atlas database. A protein- protein interaction network was then constructed and a pathway function analysis of the genes in the network was conducted. Results:PRDX1 expression was mainly localized to the cytoplasm, as well as the nucleus of cells. The expression rate of PRDX1 in epithelial ovarian malignant tissues (96.04%) was significantly higher than that in borderline (72.72%) and benign (57.14%) epithelial ovarian tumors, and normal ovarian tissue (20%; all P<0.05). Cox multivariate regression analysis indicated that advanced clinical stage, low tissue differentiation, and high expression of PRDX1 were independent risk factors affecting the prognosis of epithelial ovarian cancer (all P<0.05). Cell function assay verified that the decreased expression of PRDX1 inhibited ovarian cancer cell proliferation, invasion, and metastasis. GSEA analysis indicated that PRDX1 was significantly related to the Wnt signaling pathway. Western blot analysis confirmed that PRDX1 could regulate the expression of ?-catenin in the Wnt pathway. Conclusion:Decreased expression of PRDX1 can attenuate cell proliferation, invasion, and metastasis of ovarian cancer cells. The expression of PRDX1 is related to the prognosis of patients with ovarian cancer and can therefore be used as a biomarker.

Project description:Background: Exogenous HMGB1 plays a vital role in tumor recurrence, and HMGB1 is ubiquitous in the tumor microenvironment. However, the mechanism of action is still unclear. We investigated the role of exogenous HMGB1 in tumor proliferation and metastasis using human SW1990 and PANC-1 cells after radiotherapy and explored the possible molecular mechanism. Materials and Methods: Residual PANC-1 cells and SW1990 cells were isolated after radiotherapy. The supernatant after radiotherapy was collected. The relative expression of HMGB1 was evaluated by Enzyme Linked Immunosorbent Assay (ELISA). Electron microscope (EMS) was used to collect the images of pancreatic cancer cells pre and post radiotherapy treatment. The proliferation of pancreatic cancer cells which were treated with different radiation doses was measured by Carboxy Fluorescein Succinimidyl Ester (CFSE). The migration rates of pancreatic cancer cells were measured by wound healing assays. Subsequently, the expression of related proteins was detected by Western Blot. In vivo, the subcutaneous pancreatic tumor models of nude mice were established, and therapeutic capabilities were tested. Results: HMGB1 was detected in the supernatant of pancreatic cancer cells after radiotherapy. The results of CFSE showed that exogenous HMGB1 promotes the proliferation and metastasis of pancreatic cancer cells. The western blot results showed activation of p-GSK 3β and up-regulation of N-CA, Bcl-2, and Ki67 in response to HMGB1 stimulation, while E-CA expression was down-regulated in pancreatic cancer cells in response to HMGB1 stimulation. In vivo, ethyl pyruvate (EP, HMGB1 inhibitor) inhibits the growth of tumors and HMGB1 promotes the proliferation of tumors after radiation. Conclusion: Radiotherapy induces HMGB1 release into the extracellular space. Exogenous HMGB1 promotes the proliferation and metastasis of PANC-1 cells and SW1990 cells by activation of p-GSK 3β which is mediated by Wnt pathway.

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Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.

Publications

Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.

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