YY1 targets tubulin polymerisation-promoting protein to inhibit migration, invasion and angiogenesis in pancreatic cancer via p38/MAPK and PI3K/AKT pathways
Menée à partir de l'analyse immunohistochimique de 71 échantillons tumoraux prélevés sur des patients atteints d'un cancer du pancréas et menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel le facteur de transcription Yin Yang 1, en réduisant le niveau d'expression de la protéine TPPP via les voies de signalisation p38/MAPK et PI3K/AKT, inhibe les processus de migration et d'envahissement de la tumeur ainsi que l'angiogenèse
Background : Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated. Methods : In this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer. Results : Immunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways. Conclusion : Our study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer.