Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications.
Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications.
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DOI：
10.1016/j.gendis.2020.05.004
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发表时间：
2021-05
期刊：
影响因子：
6.8
通讯作者：
Chi JT
中科院分区：
文献类型：
--
作者：
Sun T;Chi JT
铁凋亡是一种以脂质过氧化为特征的铁依赖性细胞死亡的新形式。虽然铁凋亡症的重要性和疾病相关性正在得到认可，但关于铁凋亡症的各种遗传和非遗传决定因素仍有很多未知之处。Hippo信号通路是一种进化上保守的通路，它响应各种环境信号并控制器官大小、细胞增殖、死亡和自我更新能力。在癌症生物学中，Hippo通路是一种有效的肿瘤抑制机制，其失调有助于细胞凋亡逃避、癌症发展、转移和治疗抗性。Hippo失调导致雅普和TAZ（TEAD的两种主要转录共激活因子）的异常激活，其诱导触发肿瘤促进表型的基因的表达，包括增强的细胞增殖、自我更新和凋亡抑制。Hippo通路受细胞-细胞接触和细胞密度/汇合的调节。近年来，研究发现铁凋亡受细胞接触和密度的调节。低密度下的雅普/TAZ活化，虽然赋予凋亡抗性，但使癌细胞对铁凋亡敏感。这些发现确立了雅普/TAZ和Hippo通路作为铁凋亡的新决定因素。因此，诱导铁凋亡可能对雅普/TAZ激活的化疗耐药和转移性肿瘤细胞具有治疗潜力。反过来，临床开发中的各种雅普/TAZ靶向治疗可能会产生铁凋亡抗性，从而限制治疗效果。
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.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
DOI：
10.1126/science.aaw9872
发表时间：
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期刊：
Science (New York, N.Y.)
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影响因子：
11.4
作者：
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影响因子：
64.5
作者：
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DOI：
10.1016/j.bbrc.2020.01.066
发表时间：
2020-03-19
影响因子：
3.1
作者：
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通讯作者：
Tang, Daolin