Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications
Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis is gaining recognition, much remains unknown about various genetic and non-genetic determinants of ferroptosis. Hippo signaling pathway is an evolut...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2021-05-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220300696 |
| _version_ | 1797721807389720576 |
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| author | Tianai Sun Jen-Tsan Chi |
| author_facet | Tianai Sun Jen-Tsan Chi |
| author_sort | Tianai Sun |
| collection | DOAJ |
| description | Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis is gaining recognition, much remains unknown about various genetic and non-genetic determinants of ferroptosis. Hippo signaling pathway is an evolutionarily conserved pathway that responds to various environmental cues and controls organ size, cell proliferation, death, and self-renewal capacity. In cancer biology, Hippo pathway is a potent tumor suppressing mechanism and its dysregulation contributes to apoptosis evasion, cancer development, metastasis, and treatment resistance. Hippo dysregulation leads to aberrant activation of YAP and TAZ, the two major transcription co-activators of TEADs, that induce the expression of genes triggering tumor-promoting phenotypes, including enhanced cell proliferation, self-renewal and apoptosis inhibition. The Hippo pathway is regulated by the cell-cell contact and cellular density/confluence. Recently, ferroptosis has also been found being regulated by the cellular contact and density. The YAP/TAZ activation under low density, while confers apoptosis resistance, renders cancer cells sensitivity to ferroptosis. These findings establish YAP/TAZ and Hippo pathways as novel determinants of ferroptosis. Therefore, inducing ferroptosis may have therapeutic potential for YAP/TAZ-activated chemo-resistant and metastatic tumor cells. Reciprocally, various YAP/TAZ-targeting treatments under clinical development may confer ferroptosis resistance, limiting the therapeutic efficacy. |
| first_indexed | 2024-03-12T09:38:34Z |
| format | Article |
| id | doaj.art-d54f6cecbc4e448196adf3b98d49262c |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T09:38:34Z |
| publishDate | 2021-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-d54f6cecbc4e448196adf3b98d49262c2023-09-02T13:27:37ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422021-05-0183241249Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implicationsTianai Sun0Jen-Tsan Chi1Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, 27710, USA; Center for Genomic and Computational Biology, Duke University School of Medicine, Durham, NC, 27710, USADepartment of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, 27710, USA; Center for Genomic and Computational Biology, Duke University School of Medicine, Durham, NC, 27710, USA; Corresponding author. 101 Science Drive, DUMC 3382, CIEMAS, 2177A, Duke Medical School, Durham, NC 27708, USA.Ferroptosis is a novel form of iron-dependent cell death characterized by lipid peroxidation. While the importance and disease relevance of ferroptosis is gaining recognition, much remains unknown about various genetic and non-genetic determinants of ferroptosis. Hippo signaling pathway is an evolutionarily conserved pathway that responds to various environmental cues and controls organ size, cell proliferation, death, and self-renewal capacity. In cancer biology, Hippo pathway is a potent tumor suppressing mechanism and its dysregulation contributes to apoptosis evasion, cancer development, metastasis, and treatment resistance. Hippo dysregulation leads to aberrant activation of YAP and TAZ, the two major transcription co-activators of TEADs, that induce the expression of genes triggering tumor-promoting phenotypes, including enhanced cell proliferation, self-renewal and apoptosis inhibition. The Hippo pathway is regulated by the cell-cell contact and cellular density/confluence. Recently, ferroptosis has also been found being regulated by the cellular contact and density. The YAP/TAZ activation under low density, while confers apoptosis resistance, renders cancer cells sensitivity to ferroptosis. These findings establish YAP/TAZ and Hippo pathways as novel determinants of ferroptosis. Therefore, inducing ferroptosis may have therapeutic potential for YAP/TAZ-activated chemo-resistant and metastatic tumor cells. Reciprocally, various YAP/TAZ-targeting treatments under clinical development may confer ferroptosis resistance, limiting the therapeutic efficacy.http://www.sciencedirect.com/science/article/pii/S2352304220300696ApoptosisFerroptosisHippo pathwayTranscriptional coactivator with PDZ-binding motif (TAZ)Yes-associated protein 1 (YAP1) |
| spellingShingle | Tianai Sun Jen-Tsan Chi Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications Genes and Diseases Apoptosis Ferroptosis Hippo pathway Transcriptional coactivator with PDZ-binding motif (TAZ) Yes-associated protein 1 (YAP1) |
| title | Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications |
| title_full | Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications |
| title_fullStr | Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications |
| title_full_unstemmed | Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications |
| title_short | Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications |
| title_sort | regulation of ferroptosis in cancer cells by yap taz and hippo pathways the therapeutic implications |
| topic | Apoptosis Ferroptosis Hippo pathway Transcriptional coactivator with PDZ-binding motif (TAZ) Yes-associated protein 1 (YAP1) |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220300696 |
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