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Jun 2022 Cancer communications

Low cholesterol biosynthesis favors epithelial-to-mesenchymal transition maintenance and influences tumor molecular subtyping and disease-free survival in colon cancer patients


Aulas A, Liberatoscioli ML, Finetti P, Cabaud O, Birnbaum DJ, Usclade L, Birnbaum D, Bertucci F, Mamessier E


To metastasize, epithelial cancer cells undergo an epithelial-to-mesenchymal transition (EMT) during migration, whereupon they activate a mesenchymal-to-epithelial transition (MET) when colonizing the new niche [1]. Targeting EMT or MET inducers might thus impair the metastatic process [2, 3]. However, the identification of genes involved in epithelium-mesenchyme switches (EMS) is difficult in complex samples such as human tumors. To overcome this problem, we used spheroids of a colorectal cancer (CRC) cell line, HT29, to mimic EMS in a controlled environment. HT29 spheroids were grown without any treatment (baseline condition), exposed to StemXVivo® EMT Inducing Media Supplement, an EMT inducer, for up to 9 days (EMT condition), or exposed to the EMT inducer for 5 days then grown for 4 more days without treatment to mimic EMT followed by MET (EMT-MET condition) [4] (Figure 1A). Detailed experimental procedures are available as Supplementary Materials. In baseline condition, cells grew in dense spheroids; in EMT condition, the spheroids became loose with visible peripheral rounded cells; in EMT-MET condition, the cells grew back in dense spheroids (Figure 1B). Variation of key EMS proteins paralleled the macroscopic changes: pro-mesenchymal proteins (Fibronectin and Vimentin) were increased, while the epithelial marker Occludin was decreased in the EMT condition compared to baseline and EMT-MET conditions (Supplementary Figure S1A).