The role of Hippo pathway in ferroptosis

Xiang, Jiangxia; Jiang, Mengmeng; Du, Xing

doi:10.3389/fonc.2022.1107505

Cited by 12 publications

(8 citation statements)

References 67 publications

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“…At a high cell density, YAP activity decreases, leading to a decrease in cell sensitivity to ferroptosis. Conversely, at a low cell density, YAP activity increases, resulting in an increase in cell sensitivity to ferroptosis [38]. In hepatocellular carcinoma, the knockdown of AKR1C3 resulted in a decrease in YAP nuclear translocation, leading to the inhibition of cystine transporter SLC7A11.…”

Section: Discussionmentioning

confidence: 99%

Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling

Sun,

Chang,

Jiang

et al. 2024

Molecules

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Derived from hazelnuts, hazel leaf has been utilized in traditional folk medicine for centuries in countries such as Portugal, Sweden, and Iran. In our previous investigations, we conducted a preliminary assessment of the hazel leaf polyphenol extract (referred to as ZP) and identified nine compounds, such as kaempferol and chlorogenic acid, in its composition. ZP has shown promising properties as an antioxidant and anti-inflammatory agent. Our research has revealed that ZP has protective effects against cisplatin-induced acute kidney injury (AKI). We conducted a comprehensive examination of both the pathological and ultrastructural aspects and found that ZP effectively ameliorated renal tissue lesions and mitigated mitochondrial damage. Moreover, ZP significantly suppressed malondialdehyde levels while increasing glutathione and catalase concentrations in the kidneys of AKI-induced mice. ZP decreased the number of apoptotic cells and decreased pro-apoptotic protein expression in the kidneys of mice and human renal tubular epithelial cells (HK-2). Furthermore, treatment with ZP increased the levels of proteins marking anti-ferroptosis, such as GPX4, FTH1, and FSP1, in experiments both in vivo and in vitro. We elucidated the underlying mechanisms of ZP’s actions, revealing its inhibitory effect on Yap phosphorylation and its regulation of Lats expression, which exert a protective influence on the kidneys. Furthermore, we found that inhibiting the Hippo pathway compromised ZP’s nephroprotective effects in both in vitro and in vivo studies. In summary, this research shows that ZP exhibits renoprotective properties, effectively reducing oxidative damage, apoptosis, and ferroptosis in the kidneys by targeting the Hippo pathway.

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Section: Discussionmentioning

confidence: 99%

Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling

Sun,

Chang,

Jiang

et al. 2024

Molecules

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“…Using the E-cadherin NF2 Hippo YAP signaling pathway as an example, E-cadherin loss-of-function causes a range of mutations in cancer, with NF2 loss-of-function mutations occurring in more than three-tenths of mesothelioma ( 91 , 92 ). Mutations in the YAP gene are rarely observed in signaling pathways, however, traces of expressions of this gene are often detected ( 93 ). Mutations cause cancer cells to become more sensitive to iron fall.…”

Section: Ferroptosis and Drug Resistance Of Tumorsmentioning

confidence: 99%

Ferroptosis and EMT resistance in cancer: a comprehensive review of the interplay

Zhang,

Chen,

Ding

et al. 2024

Front. Oncol.

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Ferroptosis differs from traditional cell death mechanisms like apoptosis, necrosis, and autophagy, primarily due to its reliance on iron metabolism and the loss of glutathione peroxidase activity, leading to lipid peroxidation and cell death. The dysregulation of iron metabolism is a hallmark of various cancers, contributing to tumor progression, metastasis, and notably, drug resistance. The acquisition of mesenchymal characteristics by epithelial cells is known as Epithelial–Mesenchymal Transition (EMT), a biological process intricately linked to cancer development, promoting traits such as invasiveness, metastasis, and resistance to therapeutic interventions. EMT plays a pivotal role in cancer progression and contributes significantly to the complex dynamics of carcinogenesis. Research findings indicate that mesenchymal cancer cells exhibit greater susceptibility to ferroptosis compared to their epithelial counterparts. The induction of ferroptosis becomes more effective in eliminating drug-resistant cancer cells during the process of EMT. The interplay between ferroptosis and EMT, a process where epithelial cells transform into mobile mesenchymal cells, is crucial in understanding cancer progression. EMT is associated with increased cancer metastasis and drug resistance. The review delves into how ferroptosis and EMT influence each other, highlighting the role of key proteins like GPX4, which protects against lipid peroxidation, and its inhibition can induce ferroptosis. Conversely, increased GPX4 expression is linked to heightened resistance to ferroptosis in cancer cells. Moreover, the review discusses the implications of EMT-induced transcription factors such as Snail, Zeb1, and Twist in modulating the sensitivity of tumor cells to ferroptosis, thereby affecting drug resistance and cancer treatment outcomes. Targeting the ferroptosis pathway offers a promising therapeutic strategy, particularly for tumors resistant to conventional treatments. The induction of ferroptosis in these cells could potentially overcome drug resistance. However, translating these findings into clinical practice presents challenges, including understanding the precise mechanisms of ferroptosis induction, identifying predictive biomarkers, and optimizing combination therapies. The review underscores the need for further research to unravel the complex interactions between ferroptosis, EMT, and drug resistance in cancer. This could lead to the development of more effective, targeted cancer treatments, particularly for drug-resistant tumors, offering new hope in cancer therapeutics.

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“…The Hippo pathway, originally authenticated and elucidated in Drosophila, represented a conserved signaling pathway that regulated organ/body size by inhibiting cell proliferation and promoting apoptosis and bore considerable relevance in the suppression of cancer pathogenesis [144 ] . In the mammalian Hippo pathway, MAP4K1/2/3/4/6/7 operated simultaneously with two other STE20-like kinases, MST1/2, to phosphorylate and activate two ACG serine/threonine kinases, LATS1/2 phosphorylated and activated [145 ] . Upon phosphorylation, LATS1/2 and its splice protein MOB1A/B sequentially phosphorylated the downstream effector's YAP and TAZ.…”

Section: Proteomics In Precision Oncotherapy: Administrating Individu...mentioning

confidence: 99%

Proteomics appending a complementary dimension to precision oncotherapy

Zhou,

Zhang,

Zhou

et al. 2024

Computational and Structural Biotechnology Journal

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The role of Hippo pathway in ferroptosis

Cited by 12 publications

References 67 publications

Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling

Hazel Leaf Polyphenol Extract Alleviated Cisplatin-Induced Acute Kidney Injury by Reducing Ferroptosis through Inhibiting Hippo Signaling

Ferroptosis and EMT resistance in cancer: a comprehensive review of the interplay

Proteomics appending a complementary dimension to precision oncotherapy

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