The regulation of ferroptosis by TAZ in epithelial ovarian cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA552209 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9624690.fastq.gz | Fastqsanger.gz | |||
| SRR9624691.fastq.gz | Fastqsanger.gz | |||
| SRR9624692.fastq.gz | Fastqsanger.gz | |||
| SRR9624693.fastq.gz | Fastqsanger.gz | |||
| SRR9624694.fastq.gz | Fastqsanger.gz |
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Project description:We performed RNAseq to study the transcriptional changes of human CAOV2 ovarian cancer cells with or without TAZ silencing by siRNAs to understand the genetic determinants of ferroptosis response
2019-10-02 | GSE133664 | GEO
Project description:Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with chem-otherapy resistance representing a major therapeutic challenge. Emerging evidence suggests that ferroptosis, an iron-dependent form of regulated cell death, may selectively target chemoresistant cancer cells. Here, we identify MED12 as a critical regulator of ferroptosis sensitivity in EOC through modulation of the YAP-TEAD1 signaling pathway. Using CRISPR/Cas9-mediated knockout and rescue experiments in EOC cell lines, we demonstrate that MED12 deficiency significantly enhances sensitivity to ferroptosis in-ducers (RSL3 and Erastin), as evidenced by reduced IC50 values. Transcriptomic and chromatin accessibility analyses reveal that MED12 loss activates YAP signaling through TEAD1 upregulation, increasing chromatin accessibility at YAP-TEAD1 target loci and elevating expression of downstream effectors CYR61 and CTGF. Pharmacological inhi-bition of YAP with verteporfin or siRNA-mediated TEAD1 knockdown reverses ferrop-tosis sensitivity in MED12-deficient cells, confirming pathway specificity. These findings establish MED12 as a modulator of the YAP-TEAD1-ferroptosis axis and suggest that targeting this pathway could overcome chemoresistance in MED12-deficient EOC. Our work provides a mechanistic foundation for exploiting ferroptosis induction as a thera-peutic strategy in ovarian cancer.
2026-01-01 | GSE315125 | GEO
Project description:Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with 11 chemotherapy resistance representing a major therapeutic challenge. Emerging evidence 12 suggests that ferroptosis, an iron-dependent form of regulated cell death, may selectively 13 target chemoresistant cancer cells. Here, we identify MED12 as a critical regulator of fer- 14 roptosis sensitivity in EOC through modulation of the YAP-TEAD1 signaling pathway. 15 Using CRISPR/Cas9-mediated knockout and rescue experiments in EOC cell lines, we 16 demonstrate that MED12 deficiency significantly enhances sensitivity to ferroptosis in- 17 ducers (RSL3 and Erastin), as evidenced by reduced IC50 values. Transcriptomic and 18 chromatin accessibility analyses reveal that MED12 loss activates YAP signaling through 19 TEAD1 upregulation, increasing chromatin accessibility at YAP-TEAD1 target loci and 20 elevating expression of downstream effectors CYR61 and CTGF. Pharmacological inhibi- 21 tion of YAP with verteporfin or siRNA-mediated TEAD1 knockdown reverses ferroptosis 22 sensitivity in MED12-deficient cells, confirming pathway specificity. These findings es- 23 tablish MED12 as a modulator of the YAP-TEAD1-ferroptosis axis and suggest that tar- 24 geting this pathway could overcome chemoresistance in MED12-deficient EOC. Our work 25 provides a mechanistic foundation for exploiting ferroptosis induction as a therapeutic 26 strategy in ovarian cancer.
2026-01-01 | GSE315124 | GEO
Project description:Understanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In this study, a combination of shRNA-mediated synthetic lethality screening and transcriptomic analysis revealed the transcription factors YAP/TAZ as key drivers of Sorafenib resistance in hepatocellular carcinoma (HCC) by repressing Sorafenib-induced ferroptosis. Mechanistically, in a TEAD-dependent manner YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling HCC cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression. Our study uncovered a critical role of YAP/TAZ in the repression of ferroptosis and thus in the establishment of Sorafenib resistance in HCC, highlighting YAP/TAZ-based rewiring strategies as potential approaches to overcome HCC therapy resistance.
2021-08-20 | GSE181771 | GEO
Project description:MED12 dictates epithelial ovarian cancer cell ferroptosis sensi-tivity via YAP-TEAD1 signaling
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Project description:Ferroptosis, an emerging nonapoptotic, regulated cell death process distinguished by iron accumulation and subsequent lipid peroxidation, is intricately implicated in the development and progression of multiple cancer types. Here, we aimed to reveal that triggering ferroptosis is a promising treatment strategy for ovarian cancer. In this study, we not only validated that daphnetin caused ferroptosis, but evaluated the effects of daphnetin (and/or cisplatin) in vitro and vivo.Here, we elucidated that daphnetin, a natural product isolated from Daphne Korean Nakai, can exert antitumor effects by inducing the death and suppressing the migration of ovarian cancer cells. Subsequently, transcriptome analysis and ferroptosis inhibitor (Fer-1 and DFO) experiments revealed that there is a close correlation between daphnetin and ferroptosis in ovarian cancer. We further found that daphnetin induced ferroptosis in ovarian cancer cells, as evidenced by the accumulation of intracellular ferrous iron (Fe2+), reactive oxygen species (ROS) and lipid peroxides, as well as the depletion of glutathione (GSH) and ferroptosis indicators (SLC7A11 and GPX4). In particular, daphnetin effectively reduced the mRNA and protein levels of NQO1 (a ubiquitous flavoenzyme), and a high expression level of NQO1 was significantly associated with poor prognosis and ferroptosis resistance in ovarian cancer patients. Furthermore, NQO1 activation markedly attenuated daphnetin-induced cell death, migration and ferroptotic events in vitro and vivo. Interestingly, we also found that treatment with daphnetin, a negative regulator of NQO1, in combination with cisplatin synergistically induced ovarian cancer cell cytotoxicity. This study demonstrated that daphnetin induces ferroptosis by inhibiting NQO1 in ovarian cancer cells. Our findings identified NQO1 as a new daphnetin target and suggested that targeting NQO1 might have therapeutic effects on ovarian cancer.
2024-05-23 | GSE267812 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-10-02 | GSE133673 | GEO
Project description:TAZ, also known as WWTR1, is the one of the effectors of Hippo pathway. With its paralog, YAP, TAZ promotes organ size growth as well as tumor metastasis. In human renal carcinoma cells, we found that TAZ-silencing induces resisntance toward erastin-induced ferroptosis. In this study, TAZ is silencing in clear cell carcinoma cell line RCC4 to elucidate the downstream targets that promotes the resistance toward erastin-induced ferroptosis.
2019-09-03 | GSE121689 | GEO
Project description:Proper lung function relies on precisely balanced numbers of specialized epithelial cell types that work together and are maintained in homeostasis. We describe essential roles for the transcriptional regulators Yap and Taz, which are key effectors of Hippo pathway signaling, in maintaining lung epithelial homeostasis. We report that conditional deletion of Yap1/Yap and Wwtr1/Taz in the lung epithelium of adult mice results in severe defects with consequent animal lethality. Phenotypes associated with Yap/Taz deletion include alveolar defects and a striking development of goblet cell metaplasia throughout the airways. We performed gene expression analysis of wild type and Yap/Taz null primary mouse airway epithelial cells in order to define Yap/Taz controlled gene expression.
2021-08-09 | GSE156525 | GEO
Project description:MED12 dictates epithelial ovarian cancer cell ferroptosis sensi- 2 tivity via YAP-TEAD1 signaling
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