CRYAB Promotes Colorectal Cancer Progression by Inhibiting Ferroptosis Through Blocking TRIM55-Mediated β-Catenin Ubiquitination and Degradation.

BACKGROUND

α-Crystallin B (CRYAB) is a chaperone member of the HSPs family that protects proteins with which it interacts from degradation. This study aims to investigate the effect of CRYAB on the progression of colorectal cancer (CRC) and its underlying mechanism.

METHODS

CRYAB expression was evaluated in CRC tissues. Cell growth was tested by CCK-8 kit. Lipid reactive oxygen species (ROS) assays, lipid peroxidation assays, glutathione assays were used to assess the degree of cellular lipid peroxidation of CRC cells. The potential signal pathways of CRYAB were analyzed and verified by Western blot (WB) and immunoprecipitation (Co-IP).

RESULTS

CRYAB expression was elevated in CRC tissues and exhibited sensitivity and specificity in predicting CRC. Functionally, knockdown of CRYAB induced ferroptosis in CRC cells. Mechanistically, CRYAB binding prevented from β-catenin interacting with TRIM55, leading to an increase in β-catenin protein stability, which desensitized CRC cells to ferroptosis and ultimately accelerated cancer progression.

CONCLUSIONS

Targeting CRYAB might be a promising strategy to enhance ferroptosis and improve the efficacy of CRC therapy.