Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-33950
PROVIDER: PRJNA150029 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors
2015-08-18 | E-GEOD-33950 | ExpressionAtlas
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 common feature of many solid tumors due to aberrant proliferation and angiogenesis that is associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIFs). Identification of the long-lasting effects of hypoxia beyond the immediate HIF-induced alterations could provide a better understanding of hypoxia-driven metastasis and potential strategies to circumvent it. Here, we uncovered a hypoxia-induced mechanism that exerts a prolonged effect to promote metastasis. In breast cancer patient-derived circulating tumor cell (CTC) lines and common breast cancer cell lines, hypoxia downregulated tumor intrinsic type I interferon (IFN) signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells, via both HIF-dependent and HIF-independent mechanisms. Hypoxia induced durable IFN/AP suppression in certain cell types that was sustained after returning to normoxic conditions, presenting a “hypoxic memory” phenotype. Hypoxic memory of IFN/AP downregulation was established by specific hypoxic priming, and cells with hypoxic memory had an enhanced ability for tumorigenesis and metastasis. Overexpression of IRF3 enhanced IFN signaling and reduced tumor growth in normoxic, but not hypoxic, conditions. The histone deacetylase inhibitor (HDACi) entinostat upregulated IFN targets and erased the hypoxic memory. These results point to a mechanism by which hypoxia facilitates tumor progression through a long-lasting memory that provides advantages for CTCs during the metastatic cascade.
2024-06-28 | GSE269984 | GEO
Project description:Hypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis that is associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIFs). Identification of the long-lasting effects of hypoxia beyond the immediate HIF-induced alterations could provide a better understanding of hypoxia-driven metastasis and potential strategies to circumvent it. Here, we uncovered a hypoxia-induced mechanism that exerts a prolonged effect to promote metastasis. In breast cancer patient-derived circulating tumor cell (CTC) lines and common breast cancer cell lines, hypoxia downregulated tumor intrinsic type I interferon (IFN) signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells, via both HIF-dependent and HIF-independent mechanisms. Hypoxia induced durable IFN/AP suppression in certain cell types that was sustained after returning to normoxic conditions, presenting a “hypoxic memory” phenotype. Hypoxic memory of IFN/AP downregulation was established by specific hypoxic priming, and cells with hypoxic memory had an enhanced ability for tumorigenesis and metastasis. Overexpression of IRF3 enhanced IFN signaling and reduced tumor growth in normoxic, but not hypoxic, conditions. The histone deacetylase inhibitor (HDACi) entinostat upregulated IFN targets and erased the hypoxic memory. These results point to a mechanism by which hypoxia facilitates tumor progression through a long-lasting memory that provides advantages for CTCs during the metastatic cascade.
2024-06-28 | GSE270295 | GEO
Project description:N6-methyladenosine (m6A) modification is the most abundant internal mRNA modification in eukaryotes. Hypoxia induces reprogramming of m6A epitranscriptome, but the detail underlying regulator mechanism remains elusive in breast cancer. Here we reported that hypoxia induced elevated m6A modification involved in tumor progression. m6A- sequencing (m6A-seq) combined with RNA sequencing (RNA-seq) identified RIPOR3 as a key target gene of m6A modification under hypoxic stress. Hypoxia-induced increased of RIPOR3 m6A levels promoted its mRNA stability and expression, thereby facilitating the progression and metastasis of breast cancer. Besides, RIPOR3 was overexpressed in breast cancer cells and breast tumor tissues, and elevation of RIPOR3 expression was associated with poor prognosis. Mechanistically, RIPOR3 bound to EGFR and the interaction was enhanced under hypoxia, promoting the activation of the EGFR downstream PI3K-AKT signaling pathway. Altogether, our studies reveal that RIPOR3 responds to hypoxic stress to promote EGFR-PI3K-AKT signal pathway, facilitating breast cancer progression and metastasis, thus presenting itself as a potential therapeutic target.
2024-10-04 | GSE264247 | GEO
Project description:N6-methyladenosine (m6A) modification is the most abundant internal mRNA modification in eukaryotes. Hypoxia induces reprogramming of m6A epitranscriptome, but the detail underlying regulator mechanism remains elusive in breast cancer. Here we reported that hypoxia induced elevated m6A modification involved in tumor progression. m6A- sequencing (m6A-seq) combined with RNA sequencing (RNA-seq) identified RIPOR3 as a key target gene of m6A modification under hypoxic stress. Hypoxia-induced increased of RIPOR3 m6A levels promoted its mRNA stability and expression, thereby facilitating the progression and metastasis of breast cancer. Besides, RIPOR3 was overexpressed in breast cancer cells and breast tumor tissues, and elevation of RIPOR3 expression was associated with poor prognosis. Mechanistically, RIPOR3 bound to EGFR and the interaction was enhanced under hypoxia, promoting the activation of the EGFR downstream PI3K-AKT signaling pathway. Altogether, our studies reveal that RIPOR3 responds to hypoxic stress to promote EGFR-PI3K-AKT signal pathway, facilitating breast cancer progression and metastasis, thus presenting itself as a potential therapeutic target.
2024-10-04 | GSE264245 | GEO
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:Reciprocal interactions between breast cancer cells and the tumor microenvironment are important for cancer progression and metastasis. We report here that the deletion or inhibition of sphingosine kinase 2 (SphK2), which produces sphingosine-1-phosphate (S1P), markedly suppresses syngeneic breast tumor growth and lung metastasis in mice by creating a hostile microenvironment for tumor growth and invasion. SphK2 deficiency decreased S1P and concomitantly increased ceramides, including C16-ceramide, in stromal fibroblasts. Ceramide accumulation suppressed activation of cancer-associated fibroblasts (CAFs) by upregulating stromal p53, which restrained production of tumor-promoting factors to reprogram the tumor microenvironment and restrict breast cancer establishment. Ablation of p53 in SphK2-deficient fibroblasts reversed these effects, enabled CAF activation and promoted tumor growth and invasion. These data uncovered a novel role of SphK2 in regulating non-cell autonomous functions of p53 in stromal fibroblasts and their transition to tumor-promoting CAFs, paving the way for the development of a strategy to target the tumor microenvironment and enhance therapeutic efficacy.
2020-01-01 | GSE136655 | 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