SUN5 interacts with TRIM28, enhancing IκBα ubiquitination to promote glycolysis in colorectal cancer cells
Year: 2025
Type: article
Abstract: 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 demonstrated that the overexpression of SUN5 enhances glucose uptake and lactate production in CRC cells, whereas the opposite results are observed in SUN5-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 IκBα ubiquitination, leading to the nuclear translocation of phosphorylated P65 (phos-P65) and subsequent increases in the transcription of GLUT1 and LDHA, accelerating glycolysis. Moreover, xenograft transplantation experiments reveal that the knockdown of SUN5 inhibits glycolysis and tumorigenesis in vivo. 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.
DOI: 10.3724/abbs.2025201
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4415608341