HOXC8-activated TRIM22/NF-κB pathway promotes stemness in colorectal cancer

Colorectal cancer (CRC) remains a significant global health challenge and is characterized by high incidence and mortality rates. Although the homeobox gene family has been implicated in oncogenic processes, the precise functional role of HOXC8 in regulating CRC proliferation and stemness remains poorly defined. Cancer cells with stem-related properties, a distinct cellular subpopulation endowed with self-renewal and differentiation capacities, play pivotal roles in tumor initiation, metastasis, and therapeutic resistance. In this study, we demonstrate that HOXC8 overexpression promotes CRC cell proliferation, enhances stemness properties, and confers chemoresistance. Mechanistically, HOXC8 transcriptionally activates TRIM22, leading to the ubiquitination and degradation of IκBα, which subsequently potentiates NF-κB signaling to drive stemness maintenance in CRC cells. These findings delineate a previously unrecognized HOXC8/TRIM22/NF-κB signaling axis that critically regulates tumor progression, offering a promising molecular target for therapeutic intervention in CRC.