SUN5 interacts with TRIM28, enhancing IκBα ubiquitination to promote glycolysis in colorectal cancer cells

Glycolysis provides the main energy source for the rapid proliferation and migration of colorectal cancer (CRC) cells. In our previous studies, we reported that SUN5, a nuclear membrane protein, promotes proliferation and migration. However, whether SUN5 is involved in the process of glycolysis is unclear. Here, we demonstrate that overexpression of SUN5 enhances glucose uptake and lactate production in CRC cells, whereas the opposite results are observed in <i>SUN5</i>-knockdown cells. Mechanistically, SUN5 activates the NF-κB signaling pathway, which can be inhibited by the IKK inhibitor BAY11-7082. Further studies reveal that SUN5 interacts with TRIM28 to increase IκB <i>α</i> ubiquitination, leading to the nuclear translocation of phosphorylated P65 (phos-P65) and subsequent increases in the transcription of <i>GLUT1</i> and <i>LDHA</i>, accelerating glycolysis. Moreover, xenograft transplantation experiments reveal that the knockdown of <i>SUN5</i> inhibits glycolysis and tumorigenesis <i>in vivo</i>. Taken together, these findings indicate that SUN5 enhances the glycolysis and tumorigenesis of CRC cells via interaction with TRIM28, which provides a potential target for the diagnosis and treatment of CRC.