Dataset Information

ERO1? promotes hypoxic tumor progression and is associated with poor prognosis in pancreatic cancer.

ABSTRACT: Pancreatic cancer is a leading cause of mortality worldwide due to the difficulty of detecting early-stage disease and our poor understanding of the mediators that drive progression of hypoxic solid tumors. We therefore used a heavy isotope 'pulse/trace' proteomic approach to determine how hypoxia (Hx) alters pancreatic tumor expression of proteins that confer treatment resistance, promote metastasis, and suppress host immunity. Using this method, we identified that hypoxia stress stimulates pancreatic cancer cells to rapidly translate proteins that enhance metastasis (NOTCH2, NCS1, CD151, NUSAP1), treatment resistance (ABCB6), immune suppression (NFIL3, WDR4), angiogenesis (ANGPT4, ERO1?, FOS), alter cell metabolic activity (HK2, ENO2), and mediate growth-promoting cytokine responses (CLK3, ANGPTL4). Database mining confirmed that elevated gene expression of these hypoxia-induced mediators is significantly associated with poor patient survival in various stages of pancreatic cancer. Among these proteins, the oxidoreductase enzyme ERO1? was highly sensitive to induction by hypoxia stress across a range of different pancreatic cancer cell lines and was associated with particularly poor prognosis in human patients. Consistent with these data, genetic deletion of ERO1? substantially reduced growth rates and colony formation by pancreatic cancer cells when assessed in a series of functional assays in vitro. Accordingly, when transferred into a mouse xenograft model, ERO1?-deficient tumor cells exhibited severe growth restriction and negligible disease progression in vivo. Together, these data indicate that ERO1? is potential prognostic biomarker and novel drug target for pancreatic cancer therapy.

SUBMITTER: Gupta N

PROVIDER: S-EPMC6800261 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ERO1α promotes hypoxic tumor progression and is associated with poor prognosis in pancreatic cancer.

Gupta Nikhil N Park Jung Eun JE Tse Wilford W Low Jee Keem JK Kon Oi Lian OL McCarthy Neil N Sze Siu Kwan SK

Oncotarget 20191015 57

Pancreatic cancer is a leading cause of mortality worldwide due to the difficulty of detecting early-stage disease and our poor understanding of the mediators that drive progression of hypoxic solid tumors. We therefore used a heavy isotope 'pulse/trace' proteomic approach to determine how hypoxia (Hx) alters pancreatic tumor expression of proteins that confer treatment resistance, promote metastasis, and suppress host immunity. Using this method, we identified that hypoxia stress stimulates pan ...[more]

PMID: 31666928

Similar Datasets

Project description:PurposeCollectin subfamily member 12, a transmembrane scavenger receptor C-type lectin, is aberrantly expressed in various cancers. However, its physiological role in gastric cancer remains somewhat unclear. This study aimed to investigate the Collectin subfamily member 12 expression pattern in human gastric cancer and its role in gastric cancer progression.MethodsThe Kaplan-Meier method was used for survival analysis. The univariate and multivariate Cox proportional hazards regression models were used to identify independent predictors for progression-free survival and overall survival. The effects of Collectin subfamily member 12 on gastric cancer cell proliferation, migration, invasion, and apoptosis were detected through the cell counting kit-8 assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry analysis, respectively. Additionally, the correlation between Collectin subfamily member 12 expression and immune cell infiltration was analyzed through bioinformatics.ResultsCollectin subfamily member 12 was highly expressed in advanced gastric cancer (T3-T4, pathologic stage III-IV). High Collectin subfamily member 12 expression was correlated with a worse progression-free survival and overall survival in the gastric cancer patients. In vitro, cell line studies revealed that Collectin subfamily member 12 promoted gastric cancer cell proliferation, migration, and invasion and inhibited gastric cancer cell apoptosis. The bioinformatics analysis further demonstrated that the Collectin subfamily member 12 expression level positively correlated with infiltration of several immune cells, such as M2 macrophages, dendritic cells, neutrophils, and regulatory T cells, suggesting that Collectin subfamily member 12 may also play a role in suppressing tumor immune response in gastric cancer.ConclusionsCollectin subfamily member 12 was identified as a novel predictive marker and target for the clinical treatment of gastric cancer.

Project description:Background: MEOX1 is a homeobox transcriptional factor, and plays essential roles in regulating somite development. Our previous study indicated that MEOX1 is a critical molecular target in mesenchymal-like cancer cells in PTEN-deficient Trastuzumab resistant breast cancer. Despite the potential implication of MEOX1 for the cancer progression, no previous studies examined its level and clinical significance in lung cancer tissues. In this study, we aimed to detect the MEOX1 expression and correlate its level with clinical outcome in non-small-cell lung cancer patients (NSCLC). Methods: MEOX1 gene expression in lung cancer was examined by using the Oncomine database. MEOX1 protein levels were evaluated by IHC using the corresponding primary antibody on two different commercial lung cancer tissue arrays. siRNA knockdown was used to elucidate the function of MEOX1. Results: Analysis of the Oncomine datasets identified that an elevation of MEOX1 in gene amplification in lung cancer tissues in comparison to normal lung tissues. Immunohistochemistical analysis demonstrated that MEOX1 was localized predominantly in the nucleus, and positive rate was 67.3% (111/165) in NSCLC samples. Statistical analysis revealed high levels of MEOX1 significantly correlated with Lymph Node Metastasis and Stage. Kaplan-Meier survival analysis showed that high levels of MEOX1 were significantly associated with unfavorable survival in NSCLC patients, and MEOX1 nucleus staining had worse survival, than did patients with overall expression in lung squamous cell carcinoma patients. Multivariate Cox's regression analysis found that MEOX1 was an independent poor prognostic predictor for patients with NSCLC. Silencing of MEOX1 by specific SiRNA significantly inhibited H460 and H1299 cell proliferation and sphere formation in serum-free medium. Conclusions: Our results firstly indentified that high levels of MEOX1 especially nuclear staining was an independent prognostic factor for NSCLC, and it served a essential roles in the regulation of cell proliferation and colony formation in vitro. It may represent a potential target for the NSCLC treatment.

Dataset Information

ERO1? promotes hypoxic tumor progression and is associated with poor prognosis in pancreatic cancer.

Publications

ERO1α promotes hypoxic tumor progression and is associated with poor prognosis in pancreatic cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets