SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway

Fang, Kun; Du, Sha; Shen, Dachuan; Xiong, Zhipeng; Jiang, Ke; Liang, Dapeng; Wang, Jianxin; Xu, Huizhe; Hu, Lulu; Zhai, Xingyue; Jiang, Yuting; Xia, Zhiyu; Xie, Chunrui; Jin, Dayong; Cheng, Wei; Shao, Meng; Wang, Yifei

doi:10.1016/j.isci.2022.104618

Cited by 26 publications

(12 citation statements)

References 34 publications

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“…According to the above results, we obtained that the activation of integrin β1-FAK-YAP axis on the stiff PA gels leads to the upregulation of ACSL4 and TFRC and ultimately promotes the ferroptosis in HuH7 cells (Figure 3E). Although the involvement of YAP in ferroptosis has been demonstrated in several cancer cell types through regulation of ACSL4 and TFRC, 29,34,35 our study reveals for the first time that the ECM stiffness affects YAP-dependent ferroptosis via focal adhesion in the HCC inhibitor of YAP for 24 h and analyzes the expressions of ACSL4 and TFRC.…”

Section: ■ Introductionmentioning

confidence: 82%

Investigating the Role of Extracellular Matrix Stiffness in Modulating the Ferroptosis Process in Hepatocellular Carcinoma Cells via Scanning Electrochemical Microscopy

Zhao,

Ye,

Liu

et al. 2024

Anal. Chem.

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Extracellular matrix (ECM) stiffness modulates a variety of cellular processes, including ferroptosis, a process with significant potential implications for hepatocellular carcinoma (HCC) fibrosis and cirrhosis. However, the exact relationship between ECM stiffness and HCC ferroptosis is yet unclarified, partially due to the lack of in situ information on key parameters of the ferroptosis process of living HCC cells. This study pioneers the use of in vitro mechanical microenvironment models of HCC and the scanning electrochemical microscopy (SECM) technique for understanding this interplay. We first cultured HuH7 cells on 4.0, 18.0, and 44.0 kPa polyacrylamide (PA) gels to simulate early, intermediate, and advanced HCC ECM stiffness, respectively. Then, we used SECM to in situ monitor changes in cell membrane permeability, respiratory activity, and reactive oxygen species (ROS) levels of erastin-induced HuH7 cells on PA gels, finding that increasing ECM stiffness potentiates ferroptosis, including increased membrane permeabilization and H 2 O 2 release as well as reduced respiratory activity. Through further transcriptome sequencing and molecular biology measurements, we identified a critical role for focal adhesion kinase (FAK)-mediated yes-associated protein (YAP) in regulating the ferroptosis process dependent on ECM stiffness, which provides novel insights into the mechanical regulation of ferroptosis in HCC cells and may pave the way for innovative therapeutic strategies.

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Section: ■ Introductionmentioning

confidence: 82%

Investigating the Role of Extracellular Matrix Stiffness in Modulating the Ferroptosis Process in Hepatocellular Carcinoma Cells via Scanning Electrochemical Microscopy

Zhao,

Ye,

Liu

et al. 2024

Anal. Chem.

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“…The hippo pathway is an effective tumor-suppressor, and its abnormality contributes to apoptosis evasion of cancer cells, cancer progression, metastasis, and chemoresistance. Recent studies identified YAP/TAZ and Hippo pathways as crucial determinants of ferroptosis in several cancers including ovarian cancer, lung adenocarcinoma., breast tumors, renal cell carcinoma [25][26][27][28][29][30][31]. For example, Gao et al [32] revealed YAP/TAZ conferred the resistance of HCC cells to sorafenib via inhibiting ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

TEA Domain Transcription Factor 1 Inhibits Ferroptosis and Sorafenib Sensitivity of Hepatocellular Carcinoma Cells

Zhang

Zhao³

et al. 2023

Dig Dis Sci

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Background Ferroptosis, as a unique form of cell death, plays crucial negative roles in tumorigenesis and progression. This study aimed to investigate the role and molecular mechanism of TEA domain transcription factor 1 (TEAD1) in HCC and its effect on sorafenib-induced ferroptosis. Methods TEAD1 expression was analyzed in HCC tissues using quantitative PCR, and western blot. The effects on cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. Intracellular iron, reactive oxygen species (ROS), malondialdehyde (MDA) and GSH measurement was used to assess ferroptosis. Chromatin immunoprecipitation and luciferase reporter gene assays were performed to verify the relationship between TEAD1 and solute carrier family 3 member 2 (SLC3A2). Expression of mTOR, ribosomal protein S6, glutathione peroxidase 4 (GPX4) and SLC3A2 was analyzed by western blot. Tumor xenografts were used assess the effect of TEAD1 on tumor growth in vivo. Results TEAD1 was more abundant in HCC compared with normal tissues. Overexpression of TEAD1 enhanced the proliferation, migration, and invasion of HCC cells, while knockdown of TEAD1 inhibited these cell behaviors. Further, TEAD1 inhibited ferroptosis, which was demonstrated by decreased intracellular Fe 2+ content, ROS, and MDA levels, and increased GSH activity. Mechnistically, TEAD1 promotes the transcription of SLC3A2 and activates the mTOR signaling. Additionally, silenced TEAD1 restrained tumor growth and enhance sorafenib-induced antitumor activity in vivo. Conclusions TEAD1 confers resistance of HCC cells to ferroptosis, thereby promoting the progression of HCC, suggesting the potential value of TEAD1 in the diagnosis and treatment of HCC.

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“…Glycogen synthase kinase-3 β (GSK-3 β) promoting erastininduced ferroptosis by blocking Nrf2 in breast cancer (Wu et al, 2020). Suppressor of fused homolog (SUFU) is a key element of the Hedgehog pathway (Fang et al, 2022)…”

Section: Driving System Of Ferroptosismentioning

confidence: 99%

“…Glycogen synthase kinase-3 β (GSK-3 β) promoting erastin-induced ferroptosis by blocking Nrf2 in breast cancer ( Wu et al, 2020 ). Suppressor of fused homolog (SUFU) is a key element of the Hedgehog pathway ( Fang et al, 2022 ). The deletion of SUFU can increase the ferroptosis of breast cancer cells activated by RSL3 by decreasing ACSL4.…”

Section: The Molecules Participate In the Regulation Of Ferroptosis I...mentioning

confidence: 99%

Targeting ferroptosis, the achilles’ heel of breast cancer: A review

Liu

Hu²,

Yi³

et al. 2022

Front. Pharmacol.

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Ferroptosis is referred as a novel type of cell death discovered in recent years with the feature of the accumulation of iron-dependent lipid reactive oxygen species. Breast cancer is one of the most common malignant cancers in women. There is increasing evidence that ferroptosis can inhibit breast cancer cell growth, improve the sensitivity of chemotherapy and radiotherapy and inhibit distant metastases. Therefore, ferroptosis can be regarded a new target for tumor suppression and may expand the landscape of clinical treatment of breast cancer. This review highlights the ferroptosis mechanism and its potential role in breast cancer treatment to explore new therapeutic strategies of breast cancer.

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SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway

Cited by 26 publications

References 34 publications

Investigating the Role of Extracellular Matrix Stiffness in Modulating the Ferroptosis Process in Hepatocellular Carcinoma Cells via Scanning Electrochemical Microscopy

Investigating the Role of Extracellular Matrix Stiffness in Modulating the Ferroptosis Process in Hepatocellular Carcinoma Cells via Scanning Electrochemical Microscopy

TEA Domain Transcription Factor 1 Inhibits Ferroptosis and Sorafenib Sensitivity of Hepatocellular Carcinoma Cells

Targeting ferroptosis, the achilles’ heel of breast cancer: A review

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