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AMER1 deficiency promotes the distant metastasis of colorectal cancer by inhibiting SLC7A11- and FTL-mediated ferroptosis.
Lei, Siqin; Chen, Chaoyi; Han, Fengyan; Deng, Jingwen; Huang, Dongdong; Qian, Lili; Zhu, Ming; Ma, Xiaohui; Lai, Maode; Xu, Enping; Zhang, Honghe.
Afiliación
  • Lei S; Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.
  • Chen C; Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang Provincial Clinical Research Center for Cancer, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Center, Zheji
  • Han F; Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.
  • Deng J; Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.
  • Huang D; The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • Qian L; Cancer Center, Department of Pathology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.
  • Zhu M; Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.
  • Ma X; Pharmacology & Toxicology Research Center, The State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tasly Academy, Tasly Holding Group Co., Ltd., Tianjin 300410, China.
  • Lai M; Department of Pathology, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of the Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang U
  • Xu E; Department of Pathology, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of the Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang U
  • Zhang H; Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China; Ke
Cell Rep ; 42(9): 113110, 2023 09 26.
Article en En | MEDLINE | ID: mdl-37682704
The crosstalk between ferroptosis and cancer metastasis remains unclear. Here, we identify AMER1 as a key regulator of ferroptosis. AMER1 loss causes resistance to ferroptosis in colorectal cancer (CRC) cells. Interestingly, AMER1-deficient CRC cells preferentially form distant metastases, while AMER1-naive CRC cells mainly invade lymph nodes. Moreover, the ferroptosis inhibitor liproxstatin-1 effectively promotes hematogenous transfer of AMER1-naive cells. Mechanistically, AMER1 binds to SLC7A11 and ferritin light chain (FTL) and recruits ß-TrCP1/2, which degrade SLC7A11 and FTL by ubiquitination. Therefore, AMER1 deficiency increases cellular cystine levels but decreases the pool of labile free iron, thereby enhancing resistance to ferroptosis in CRC cells. Thus, AMER1 deficiency increases the survival of CRC cells in the blood under conditions of high oxidative stress and then promotes hematogenous metastasis of CRC. In conclusion, AMER1 mediates the crosstalk between ferroptosis and cancer metastasis, which provides a window of opportunity for treating metastatic colorectal cancer patients with AMER1 mutations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Neoplasias del Colon / Ferroptosis Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Neoplasias del Colon / Ferroptosis Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos