E-GEOD-33950
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA150029
PROVIDER: E-GEOD-33950 | ExpressionAtlas | 2015-08-18
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors
| PRJNA150029 | ENA
Project description:Coactivator associated arginine methyltransferase 1 has been reported to play paramount roles in estrogen receptor alpha (ERα)-positive breast cancer. It promotes breast cancer development and metastasis. However, little research about CARM1 has been focused on triple-negative breast cancer (TNBC). Here, we report that CARM1 promotes proliferation, epithelial-mesenchymal transition (EMT) and stemness in TNBC. CARM1 transactivates Hypoxia-inducible factor 1 subunit alpha (HIF1A) and is physically associated with it. They function together in a concerted complex to regulate downstream targets and promote the carcinogenesis and metastasis of TNBC.
2024-02-24 | GSE167394 | GEO
Project description:Through integrative analysis of clinical breast cancer gene expression datasets, cell line models of breast cancer progression, and mutation data from cancer genome resequencing studies, we have identified RNA binding motif protein 47 (RBM47) as a candidate suppressor of breast cancer metastasis. RBM47 inhibited breast cancer progression in experimental models. Transcriptome-wide analysis of RBM47 localization by HITS-CLIP revealed widespread binding to mRNAs, preferentially at the 3' UTRs. RBM47 altered the abundance of a subset of its target mRNAs. Some of the mRNAs stabilized by RBM47, as exemplified by dickkopf WNT signaling pathway inhibitor 1 (DKK1), mediate tumor suppressive effects downstream of RBM47. This work identifies RBM47 as a suppressor of breast cancer progression and highlights the potential of global RNA modulatory events as a source of metastasis-promoting phenotypic traits. Cancer cells transduced with doxycycline-inducible wildtype RBM47 or the RBM47-I281fs mutant, treated with increasing concentrations of doxycycline.
2014-06-11 | E-GEOD-53779 | biostudies-arrayexpress
Project description:Metastasis is responsible for the majority of breast cancer (BrCa) deaths; however, the underlying mechanisms remain largely elusive. Here, we report that suppression of MBD2 alternative splicing under hypoxia, which favors the production of MBD2a, facilitates BrCa metastasis. Specifically, we found that MBD2a promotes, whereas its less-known short form MBD2c suppresses metastasis. We elucidate that HIF-1 activation under hypoxia facilitates MBD2a production via repression of SRSF2-mediated alternative splicing and, as a result, the elevated MBD2a outcompetes MBD2c for binding to the promoter CpG islands to activate the expression of FZD1, thereby promoting EMT and metastasis. Strikingly, clinical data reveals significantly correlated expression pattern of MBD2a and MBD2c with the invasiveness of malignancy, indicating the opposing roles for MBD2 splicing variants in regulating human BrCa metastasis. Thus, our findings establish a novel link between MBD2 switching and tumor metastasis, and provide promising therapeutic strategy and predictive biomarkers for hypoxia-driven BrCa metastasis.
2021-02-01 | GSE151952 | GEO
Project description:Hypoxia is a hallmark of cancer development. However, the molecular mechanisms by which hypoxia promotes tumor metastasis are not fully understood. In this study, we demonstrate that hypoxia promotes breast cancer metastasis through suppression of ΔNp63α-dependent in a HIF1α-independent manner. We show that hypoxia activates unfolded protein response (UPR) to elevate XBP1s, which in turn forms stable repressor protein complexes with HDAC2 and EZH2 in suppression of ΔNp63α. Notably, while H3K27ac is predominantly presented in the ΔNp63 promoter under normoxia, it is switched to H3K27me3 under hypoxia. We show that XBP1s binds to the ΔNp63 promoter to recruit HDAC2 and EZH2 in facilitating the H3K27ac-H3K27me3 switch. Knockdown or pharmacological inhibition of either HDAC2 or EZH2 leads to increased H3K27ac concomitant with reduced H3K27me3, which effectively restores ΔNp63α expression suppressed by hypoxia, resulting in inhibition of cell migration. Clinical analyses reveal that reduced p63 expression is correlated with the elevated expression of XBP1, HDAC2, or EZH2, and is associated with poor overall survival in human breast cancer patients. Together, these results indicate that hypoxia-activated XBP1s modulates the epigenetic program in suppression of ΔNp63α to promote breast cancer metastasis independent of HIF1α and provides a molecule basis for targeting the XBP1s/HDAC2/EZH2-ΔNp63α axis as a putative strategy in the treatment of breast cancer metastasis.
2024-01-24 | GSE253833 | GEO
Project description:Calreticulin (CALR) is a multi-functional protein that participates in various cellular processes, which include calcium homeostasis, cell adhesion, protein folding and cancer progression. However, the role of CALR in breast cancer is unclear. Here we report that CALR is overexpressed in breast cancer compared with normal tissue, and its expression is correlated with patient mortality and stemness indices. CALR expression was increased in mammosphere cultures, CD24-CD44+ subsets and ALDH+ subsets, which are enriched for breast cancer stem cells (BCSCs). Additionally, CALR knockdown led to BCSC depletion, which impaired tumor initiation and metastasis, and enhanced chemosensitivity in vivo. Chromatinimmunoprecipitation and reporter assays revealed that hypoxia-inducible factor 1 (HIF-1) directly activated CALR transcription in hypoxic breast cancer cells. CALR expression was correlated with Wnt/β-catenin pathway activation and an activator of Wnt/β-catenin signaling abrogated the inhibitory effect of CALR knockdown on mammosphere formation. Taken together, our results demonstrate that CALRfacilitates breast cancer progression by promoting the BCSC phenotype through Wnt/β-catenin signaling in a HIF-1-dependent manner, and suggest that CALR may represent a novel target for breast cancer therapy.
2021-11-16 | GSE181431 | GEO
Project description:RanBP2 type and C3HC4 type zinc finger containing protein 1 (RBCK1,) is a 58 kDa protein containing N-terminal ubiquitin like (UBL) domain, npl4 type zinc finger (NZF) domain and catalytic carbon terminal RBR domain. It is known that it has abnormal expression in tumors, making it a valuable diagnostic marker and drug target. A large number of studies have confirmed that in ER positive breast cancer, about 25%-40% of the tumor showed a visible hypoxia area. Under hypoxia, tumor cells can activate HIF1 pathway and widely activate the expression of downstream genes. Hypoxia inducible factor HIF-1 is composed of HIF-1α and HIF-1β Two subunits, The protein level of HIF-1α is precisely regulated by oxygen concentration. Here, we report RBCK1, a RING family ubiquitin ligase that regulates HIF1α, promoting ER positive breast cancer growth and inhibiting apoptosis. Deletion of RBCK1 inhibits ER positive breast cancer growth and promotes cell death. RNA sequencing analysis showed that in ER positive breast cancer, RBCK1 may be an important modifier of HIF1α signal pathway. Further experiments showed that RBCK1 and HIF1α Interacts and inhibits HIF1α polyubiquitination to inhibit HIF1α degradation in ER positive breast cancer cells. These finding reveals a novel direct HIF1α regulator and a potential therapeutic target for ER positive breast cancer.
2022-02-12 | GSE196274 | GEO
Project description:The consequence of a supra-physiological folate tumour microenvironment in promoting metastasis potential of human breast cancers remains unexplored. This study examined the molecular mechanism by which clinically aberrant folate levels may promote mitochondria and glycolytic stress-associated proteomic signatures to promote metastasis potential of human MCF-7 breast cancer cells.
2022-11-21 | PXD011046 | Pride
Project description:Liver cancer is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with liver cancer. Hypoxia is a common feature of solid tumors and enhances malignant character of cancer cells. However, the exact mechanisms involved in hypoxia-driven liver cancer progression and metastasis have not been well clarified so far. The aim of this study was to investigate the contribution of long non-coding RNA (lncRNA) in hypoxia promoting liver cancer progression. We screened and revealed LINC00839 as a novel hypoxia-responsive lncRNA in liver cancer. LINC00839 expression was up-regulated in liver cancer tissues and cell lines, and the patients with high LINC00839 expression had shortened overall survival. LINC00839 further overexpressed under hypoxia and promoted liver cancer cell proliferation, migration, and invasion. Mechanistically, LINC00839 bound multiple proteins that were primarily associated with the metabolism and RNA transport, and positively regulated the expression of Formin-like protein 2 (FMNL2). LINC00839 could promote hypoxia-mediated liver cancer progression, suggesting it may be a clinically valuable biomarker and serve as a molecular target for the diagnosis, prognosis, and therapy of liver cancer.
2023-03-11 | PXD034526 | Pride
Project description:Interleukin (IL-6) is a pleotropic cytokine with both tumor-promoting and -inhibitory effects on breast cancer growth. However, the mechanisms governing the outcome of IL-6 on cancer progression remain to be clarified. Our study unraveled a novel long noncoding RNA (lncRNA)-AU021063 downstream of IL-6 signaling. We found that IL-6 induced the expression of lncRNA-AU021063 predominantly in breast cancer compared to other cancer types. Mechanistically, IL-6 induced AT-rich interactive domain 5a (Arid5a) expression, which promotes the transcription of lncRNA-AU021063. In turn, lncRNA-AU021063 promotes breast cancer metastasis through stabilizing tribbles homolog 3 (Trib3) and activating Mek/Erk signaling pathway. Genetic ablation of either Arid5a, lncRNA-AU021063 or Trib3 abolished breast cancer metastasis in vitro and in vivo. Overall, our study highlights the importance of IL-6-Arid5a-lncRNA-AU021063 axis in regulating breast cancer invasiveness and metastasis, which may provide potential novel therapeutics for breast cancer.
2021-08-19 | GSE178250 | GEO