SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway
Summary: Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Cancer cells differ in their sensitivity to ferroptosis. Here we showed that the Suppressor of fused homolog (SUFU), a critical component in Hedgehog signaling, regulates fer...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222008902 |
| _version_ | 1811334994331697152 |
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| author | Kun Fang Sha Du Dachuan Shen Zhipeng Xiong Ke Jiang Dapeng Liang Jianxin Wang Huizhe Xu Lulu Hu Xingyue Zhai Yuting Jiang Zhiyu Xia Chunrui Xie Di Jin Wei Cheng Songshu Meng Yifei Wang |
| author_facet | Kun Fang Sha Du Dachuan Shen Zhipeng Xiong Ke Jiang Dapeng Liang Jianxin Wang Huizhe Xu Lulu Hu Xingyue Zhai Yuting Jiang Zhiyu Xia Chunrui Xie Di Jin Wei Cheng Songshu Meng Yifei Wang |
| author_sort | Kun Fang |
| collection | DOAJ |
| description | Summary: Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Cancer cells differ in their sensitivity to ferroptosis. Here we showed that the Suppressor of fused homolog (SUFU), a critical component in Hedgehog signaling, regulates ferroptosis sensitivity of breast cancer cells. Ectopic SUFU expression suppressed, whereas depletion of SUFU enhanced the sensitivity of breast cancer cells to RSL3-triggered ferroptosis through deregulation of ACSL4. Moreover, SUFU depletion promoted the activation of Yes-associated protein (YAP), thereby increasing the expression of ACSL4. Mechanistically, SUFU is associated with LATS1. Deletion of a region comprising residues 174–385 in SUFU disrupted SUFU binding to LATS1, thus abrogating SUFU-mediated downregulation of the YAP-ACSL4 axis and sensitivity to ferroptosis. Noteworthy, we showed that vincristine downregulated SUFU, thus increasing breast cancer cell sensitivity to RSL3 in vitro and in vivo. Together, our findings uncover SUFU as a novel regulator in ferroptosis sensitivity. |
| first_indexed | 2024-04-13T17:17:24Z |
| format | Article |
| id | doaj.art-3e22ae84788c498681f7e4a2b41898cb |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T17:17:24Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3e22ae84788c498681f7e4a2b41898cb2022-12-22T02:38:05ZengElsevieriScience2589-00422022-07-01257104618SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathwayKun Fang0Sha Du1Dachuan Shen2Zhipeng Xiong3Ke Jiang4Dapeng Liang5Jianxin Wang6Huizhe Xu7Lulu Hu8Xingyue Zhai9Yuting Jiang10Zhiyu Xia11Chunrui Xie12Di Jin13Wei Cheng14Songshu Meng15Yifei Wang16Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China; Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaDepartment of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaCenter for Single-Cell Omics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaCentral Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, ChinaDepartment of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao University, Qingdao 266000, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, ChinaInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, China; Corresponding authorInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, China; Corresponding authorInstitute of Cancer Stem Cell, Dalian Medical University Cancer Center, No. 9 West Section, South Lvshun Road, Dalian 116044, China; Corresponding authorDepartment of Obstetrics and Gynecology, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China; Corresponding authorSummary: Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Cancer cells differ in their sensitivity to ferroptosis. Here we showed that the Suppressor of fused homolog (SUFU), a critical component in Hedgehog signaling, regulates ferroptosis sensitivity of breast cancer cells. Ectopic SUFU expression suppressed, whereas depletion of SUFU enhanced the sensitivity of breast cancer cells to RSL3-triggered ferroptosis through deregulation of ACSL4. Moreover, SUFU depletion promoted the activation of Yes-associated protein (YAP), thereby increasing the expression of ACSL4. Mechanistically, SUFU is associated with LATS1. Deletion of a region comprising residues 174–385 in SUFU disrupted SUFU binding to LATS1, thus abrogating SUFU-mediated downregulation of the YAP-ACSL4 axis and sensitivity to ferroptosis. Noteworthy, we showed that vincristine downregulated SUFU, thus increasing breast cancer cell sensitivity to RSL3 in vitro and in vivo. Together, our findings uncover SUFU as a novel regulator in ferroptosis sensitivity.http://www.sciencedirect.com/science/article/pii/S2589004222008902Cell biologyFunctional aspects of cell biologyCancer |
| spellingShingle | Kun Fang Sha Du Dachuan Shen Zhipeng Xiong Ke Jiang Dapeng Liang Jianxin Wang Huizhe Xu Lulu Hu Xingyue Zhai Yuting Jiang Zhiyu Xia Chunrui Xie Di Jin Wei Cheng Songshu Meng Yifei Wang SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway iScience Cell biology Functional aspects of cell biology Cancer |
| title | SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway |
| title_full | SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway |
| title_fullStr | SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway |
| title_full_unstemmed | SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway |
| title_short | SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway |
| title_sort | sufu suppresses ferroptosis sensitivity in breast cancer cells via hippo yap pathway |
| topic | Cell biology Functional aspects of cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222008902 |
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