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AMER1 deficiency promotes the distant metastasis of colorectal cancer by inhibiting SLC7A11- and FTL-mediated ferroptosis.

Published:26 September 2023 DOI: 10.1016/j.celrep.2023.113110 PMID: 37682704
Siqin Lei, Chaoyi Chen, Fengyan Han, Jingwen Deng, Dongdong Huang, Lili Qian, Ming Zhu, Xiaohui Ma, Maode Lai, Enping Xu, Honghe Zhang

Abstract

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 β-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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Materials Related products
Procduct Name CAS Molecular Formula Supplier Price
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
Necrostatin-1 4311-88-0 C13H13N3OS 258 suppliers $12.00-$2008.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00

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