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.

Ferroptosis是铁依赖性细胞死亡的一种新型形式，其特征是脂质过氧化作用。尽管人们越来越认识到肥大症的重要性和疾病相关性，但关于肥大症​​的各种遗传和非遗传决定因素仍然未知。河马信号传导途径是一种进化保守的途径，可响应各种环境线索并控制器官大小，细胞增殖，死亡和自我更新能力。在癌症生物学中，Hippo途径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，转移和治疗耐药性。河马失调导致TEAP的两个主要转录共激活因子YAP和TAZ异常激活，它们诱导触发促肿瘤表型的基因表达，包括增强的细胞增殖，自我更新和细胞凋亡抑制作用。河马途径受细胞间接触和细胞密度/汇合度的调节。最近，还发现受精症受细胞接触和密度的调节。在低密度下，YAP / TAZ激活可赋予细胞凋亡抗性，从而使癌细胞对肥大症敏感。这些发现建立了YAP / TAZ和Hippo途径，成为铁素体病的新决定因素。因此，诱导ferroptosis可能具有YAP / TAZ激活的化学耐药性和转移性肿瘤细胞的治疗潜力。相应地，临床开发中的各种以YAP / TAZ为靶标的治疗方法可能赋予抗铁锈病性，从而限制了治疗效果。河马途径受细胞间接触和细胞密度/汇合度的调节。最近，还发现受精症受细胞接触和密度的调节。在低密度下，YAP / TAZ激活可赋予细胞凋亡抗性，从而使癌细胞对肥大症敏感。这些发现建立了YAP / TAZ和Hippo途径，成为铁素体病的新决定因素。因此，诱导ferroptosis可能具有YAP / TAZ激活的化学耐药性和转移性肿瘤细胞的治疗潜力。相应地，临床开发中的各种以YAP / TAZ为靶标的治疗方法可能赋予抗铁锈病性，从而限制了治疗效果。河马途径受细胞间接触和细胞密度/汇合度的调节。最近，还发现受精症受细胞接触和密度的调节。在低密度下，YAP / TAZ激活可赋予细胞凋亡抗性，从而使癌细胞对肥大症敏感。这些发现建立了YAP / TAZ和Hippo途径，成为铁素体病的新决定因素。因此，诱导ferroptosis可能具有YAP / TAZ激活的化学耐药性和转移性肿瘤细胞的治疗潜力。相应地，临床开发中的各种以YAP / TAZ为靶标的治疗方法可能赋予抗铁锈病性，从而限制了治疗效果。同时赋予细胞凋亡抗性，使癌细胞对肥大症敏感。这些发现建立了YAP / TAZ和Hippo途径，成为铁素体病的新决定因素。因此，诱导ferroptosis可能具有YAP / TAZ激活的化学耐药性和转移性肿瘤细胞的治疗潜力。相应地，临床开发中的各种以YAP / TAZ为靶标的治疗方法可能赋予抗铁锈病性，从而限制了治疗效果。同时赋予细胞凋亡抗性，使癌细胞对肥大症敏感。这些发现建立了YAP / TAZ和Hippo途径，成为铁素体病的新决定因素。因此，诱导ferroptosis可能具有YAP / TAZ激活的化学耐药性和转移性肿瘤细胞的治疗潜力。相应地，临床开发中的各种以YAP / TAZ为靶标的治疗方法可能赋予抗铁锈病性，从而限制了治疗效果。