β-arrestin1 inhibits ferroptosis in colorectal cancer cells by modulating p53/SLC7A11 signaling

Abstract Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive system, and ARRB1(β-arrestin1) plays a crucial role in regulating the proliferation, invasion, migration, and other aspects of tumor cells. However, the role and regulatory mechanisms of ARRB1 in CRC have not been investigated. This study aims to investigate the molecular mechanisms by which ARRB1 affects the occurrence and development of CRC. The TCGA database was used to analyze the expression of ARRB1 in CRC. Cell proliferation, percentage of viable cells, migration, invasion, mitochondrial ferroptosischaracteristics, and expression of ARRB1, p53, GPX4, and SLC7A11 were analyzed by CCK8, flow cytometry, cell cloning, scratch assay, Transwell assay, transmission electron microscopy, qRT-PCR, and Western blot, respectively. The overexpression of ARRB1 decreased the percentage of viable cells and induced cellular ROS generation in CRC cells, and the ferroptosis inducer RSL3 promoted the effects of ARRB1 overexpression on the percentage of viable cells and ROS generation. Moreover, overexpression of ARRB1 promoted CRC cell p53 nuclear translocation, inhibited CRC cell proliferation, migration, and invasion, and decreased the levels of GPX4, GSH, and SLC7A11. However, si-TP53 inhibited the above effects of ARRB1 on cells. Up-regulation of ARRB1 promotes ferroptosis in colorectal cancer cells through p53/SLC7A11 signaling.