<scp>FAM118B</scp> Promotes Colorectal Carcinogenesis Through a Novel Mechanism Involving Enhanced <scp>RelA</scp> Transactivation and Subsequent <scp>SELENOF‐</scp> Dependent Glycolytic Activity

Metabolic reprogramming is a key feature of colorectal cancer (CRC), but its regulatory mechanisms remain poorly understood. This study identifies the previously uncharacterized protein FAM118B as a critical driver of CRC pathogenesis by modulating glycolytic metabolism. FAM118B was markedly upregulated in CRC tissues and was associated with poor patient prognosis. Functional assays showed that FAM118B stimulates CRC cell growth, migration, and colony formation while inhibiting apoptosis. Mechanistically, FAM118B enhanced the transcriptional activity of NF-κB subunit RelA, which directly binds to the promoter of selenoprotein F (SELENOF) and increases its expression. Elevated SELENOF promotes the expression of major glycolytic enzymes, including HK2, LDHA, and PKM2, leading to enhanced glycolytic activity. The functional significance of this axis was confirmed by the partial reversal of FAM118B-induced glycolytic activity and proliferation upon SELENOF knockdown. In vivo, FAM118B silencing markedly attenuated tumor growth in xenograft models. Collectively, our findings delineate a novel FAM118B-RelA-SELENOF signaling axis that fuels CRC progression by reprogramming cellular glycolysis, positioning FAM118B as a pivotal molecular player in CRC metabolism.