A novel ALG10/TGF-β positive regulatory loop contributes to the stemness of colorectal cancer.

The roles of asparagine-linked glycosylation (ALG) members in tumorigenic process have been widely explored. However, their effects in colorectal cancer progression are still confusing. Here, we screened 12 ALGs' expression through online datasets and found that was mostly upregulated in colorectal cancer tissues. We found that knockdown significantly suppressed the expression of stemness markers, ALDH activity, and sphere-formation ability. tumorigenic analysis indicated that knockdown attenuated the tumor-initiating ability and chemoresistance of colorectal cancer cells. Further mechanistic studies showed that knockdown suppressed the activity of TGF-β signaling by reducing TGFBR2 glycosylation, which was necessary for -mediated effects on colorectal cancer stemness; Conversely, TGF-β signaling activated gene promoter activity through Smad2's binding to gene promoter and TGF-β signaling promoted the stemness of colorectal cancer cells in an -dependent manner. This work identified a novel /TGF-β positive regulatory loop responsible for colorectal cancer stemness.