The Role Of The TIPE2 In The Progress Of Colorectal Cancer

As a negative regulator of immunity,TIPE2 plays a crucial role in innate immunity and acquired immunity.Meanwhile,TIPE2 is an ideal cancer marker and tumor suppressor molecule.From the pathological samples of colorectal cancer,we found that TIPE2 was higher expressed in the cancer tissues compared with the adjacent tissues,whereas TIPE2 was absence in colorectal cancer cell lines.To do further research on TIPE2 and colorectal cancer,we constructed AOM/DSS mice colorectal cancer model.The results show that TIPE2^+/+mice have higher tumor incidence than TIPE2^-/-mice,the former suffer more weight loss and higher tumor size and number.These results conflicted with the conclusion which TIPE2 is a tumor suppressor molecule.We speculated whether it was the effect of modeling method,then we established DSS-induced acute colitis models.The results showed that TIPE2^-/-mice was assistant with experiment colitis.Then we found that the ubiquitination of TIPE2 was mainly modified by k63,which suggested that the ubiquitination of TIPE2 was related to its activity or signal transmission.The previous mass spectrometry studies in our laboratory show that 14-3-3 family proteins were correlated with TIPE2,so we investigated the influence of 14-3-3 on TIPE2 ubiquitination and found that the expression of 14-3-3 sigma could reduce the ubiquitination of TIPE2.Therefore,we speculated whether there was a direct interaction between TIPE2 and 14-3-3 sigma.However,no direct interaction between TIPE2 and 14-3-3 sigma was found through immunofluorescence co-localization analysis and immunoprecipitation.In summary,our study found that 14-3-3 sigma could inhibit the ubiquitination of TIPE2.In the AOM/DSS colorectal cancer model,the absence of TIPE2 could reduce the tumorigenesis rate,the molecular mechanism of which needs further investigation.In addition,we will explore the how inhibition of 14-3-3 sigma on ubiquitination of TIPE2modifies the protein function of TIPE2 and its effect on the development of colorectal cancer.