SOX2-OT induced by PAI-1 promotes triple-negative breast cancer cells metastasis
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ABSTRACT:
PROVIDER: PRJNA751053 | ENA |
REPOSITORIES: ENA
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Project description:Triple-negative breast cancer (TNBC) has a relatively aggressive biological behavior and poor outcome. Our published study showed that PAI-1 could induce the migration and metastasis of TNBC cells. However, the underlying mechanism by which PAI-1 regulates TNBC metastasis has not been addressed. Using microarray analysis of lncRNA expression profiles, we identified a lncRNA SOX2-OT, which is by induced by PAI-1 and could function as an oncogenic lncRNA in TNBC.
2024-05-15 | GSE181202 | GEO
Project description:Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial. Here, using two independent TNBC models, we report a discrete subpopulation of highly metastatic SOX2/OCT4+ cells within primary tumors that exhibit elevated intracellular copper levels and marked sensitivity to TM. Global proteomic and metabolomic profiling identified TM-mediated inactivation of Complex IV as the primary metabolic defect in the SOX2/OCT4+ cell population. We identified the AMPK/mTORC1 energy sensor as an important downstream pathway and show that AMPK inhibition rescues TM-mediated loss of invasion. Furthermore, loss of the mitochondria-specific copper chaperone, COX17, restricted copper deficiency to mitochondria and phenocopied TM-mediated alterations. These findings identify a novel copper-metabolism-metastasis axis with potential to enrich patient populations in next-generation therapeutic trials.
2021-10-26 | PXD027089 | Pride
Project description:This study explored the expression, biological function and prognostic role of SOX2 in triple negative breast cancer (TNBC). Quantitative real-time PCR and immunohistochemistry were used to detect the expression of SOX2 in TNBC cell lines and clinical tissues. MTT assay, Transwell assay, flow cytometry and xenograft mouse model were used to assess the biological functions of SOX2. It was found that SOX2 was up-regulated in both TNBC cell lines and clinical tissues. High expression of SOX2 was associated with shorter overall survival and disease free survival. Moreover, inhibition of SOX2 suppressed cell proliferation and invasion, induced cell apoptosis in vitro, and suppressed tumorigenesis and metastasis in vivo. In addition, analysis of TNM stage and lymph nodes infiltration among the 237 TNBC patients by paired ?2 test showed that SOX2 was inversely correlated with tumor status, our findings provided evidence that SOX2 acts as a tumor promoter in TNBC and inhibition of SOX2 could be a potential therapeutic strategy for TNBC.
| S-EPMC6110877 | biostudies-literature
Project description:Triple therapy reduced metastasis in triple-negative breast cancer.
| PRJNA832953 | ENA
Project description:Metastasis in triple-negative breast cancer
| PRJNA437929 | ENA
Project description:Purpose: To understand the underlying mechanisms of oncolytic virus therapy in breast cancer. Methods: The primary tumors of 4T1 in BALB/C mice were exstracted and analyzed by RNA-seq. Results: In consistent with previous studies, we found some anti-tumor factors were up-regulated. Interestingly, several immunosupressive genes were activited. Conclusion: Our study identified the intercellular and intracellular factors restricting the optimized oHSV efficacy and supported the rationally designed triple therapy for clinical translation.
2023-05-01 | GSE201760 | GEO
Project description:Sox2 has been studied in several types of human solid tumors. The investigators found that Sox2 had higher expression level in colorectal cancer and metastatic tissues than normal tissues. So the investigators assumed that whether Sox2 plays an important role in the progression and migration of colon cancer.
| 2124687 | ecrin-mdr-crc
Project description:This microarray dataset contains 51 triple-negative breast cancers with clinical and recurrence information for at least 3 years of follow-up and 106 luminal breast cancers (reanalyzed data from Series GSE24124, GSE9309, and GSE17040). A novel set of 45-gene signature that was statistically predictive of distant metastasis recurrence for triple-negative breast cancer was identified in this study.
2012-11-01 | GSE33926 | GEO
Project description:We are studying the role of PAI-1 in hypergastrinemic transgenic mice (PAI-1 knockout, HK-ATPase beta knockout and corresponding control strains). As a model of hypergastrinaemia, HK-ATPase beta knockout mice are preferred instead of giving a high dose of proton pump inhibitors daily. We have successfully crossed these two strains and generated double knockout mice (PAI-1--/HK-ATPase--) and 3 different control groups (PAI-1++/HK-ATPase++, PAI-1--/HK-ATPase++ and PAI-1++/HK-ATPase--) (9 animals in each group). The gastric phenotype of all mice has been examined by morphologic and molecular analysis after 12 months. Gastric biopsies and blood samples have been taken for histology, large scale gene expression analysis, verification of mRNA and protein expression and gastrin measurements. Global gene expression analysis has been done on gastric mucosal samples from all groups of mice. The differences between wild type mice and the transgenic animals are expected to provide novel hypotheses on the role of PAI-1 in gastrin-induced changes in the gastric mucosa.
2016-02-01 | E-MTAB-3853 | biostudies-arrayexpress
Project description:Desulfosporosinus sp. OT genome sequencing
| PRJNA61253 | ENA