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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http://dx.doi.org/10.1016/j.celrep.2023.113110 | DOI Listing |
Front Pharmacol
January 2025
The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Background: Polydatin (3,4',5-trihydroxy-3-β-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy is the first-line treatment for metastatic and recurrent colorectal cancer (CRC). However, the lack of selectivity for normal cells often results in side effects.
View Article and Find Full Text PDFBiochem Biophys Rep
March 2025
Shenzhen Nucleus Gene Technology Co., Ltd., Shenzhen, 518071, China.
Colorectal cancer (CRC) is a common malignant cancer. Epoxide hydrolases (EHs) are involved in the development of cancer by regulating epoxides, but their relationship with CRC is unclear. We used multiple datasets to confirm the expression of different EPHX family members in CRC tissues, and to explore their association with different clinicopathologic characteristics.
View Article and Find Full Text PDFPol J Pathol
January 2025
Department of Pathology, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.
Cancer stem cells (CSCs) are cancer cells responsible for cancer initiation, growth, metastasis, recurrence and resistance to treatment. OCT4 and c-MYC are widely accepted as CSC markers. In this study, we examined the immunohistochemical co-expression of c-MYC and OCT4 with Ki-67 in colorectal cancers (CRC) and the relationship between the results and prognostic and therapeutic data.
View Article and Find Full Text PDFJ Hematol Oncol
January 2025
Center for Cell Therapy & Regenerative Medicine (CCRG), Antwerp University Hospital (UZA), Edegem, Belgium.
Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms' tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months.
View Article and Find Full Text PDFBMC Cancer
January 2025
Laboratory of Molecular Genetics, National Cancer Center Research Institute, Tokyo, Japan.
Background: This study aimed to analyze the functional role of Brd4 in colorectal cancer (CRC) organoids. Brd4 was identified as a CRC-related gene by our previous Sleeping Beauty mutagenesis transposon screening in mice. Brd4 is a transcriptional regulator that recognizes acetylated histones and is known to be involved in inflammatory responses.
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