<scp>CD39</scp> Contributes to the Ability of Cell Invasion in Heterogeneity of Colorectal Cancer

Tumour heterogeneity will accumulate and amplify during cell culture and passage, even if derived from the same strain. In the current study, multiple batches of colorectal cancer HCT116 and HT29 cell lines were obtained using different conditions of trypsin digestion and processed for RNA sequencing. CD39 was identified as a biomarker highly expressed in easily trypsin-digested cells compared to the undigestible ones. Furthermore, CD39 was determined to enhance cell invasion and suppress cell apoptosis but not affect cell proliferation. Moreover, CD39 could activate the TGF-β/SMAD3 signalling pathway, whereas the expression of CD39 was negatively regulated by SMAD3 via recruitment of SETDB1 and adding H3K9me3 to the CD39 promoter in HCT116 cells. Overall, our study uncovered distinct gene signatures amongst different heterogeneities of colorectal cells and revealed the effect of CD39 on cell invasion and apoptosis, as well as determined the epigenetic role in regulating CD39 transcription.