COL17A1-KO CRC organoids expressed LGR5 but lost the expression of p27 in a similar way as it occurred in COL17A1-wild-type (WT) organoids, indicating that type XVII collagen regulated p27 expression independently from LGR5. COL17A1-KO organoids were more susceptible to chemotherapy treatment, suggesting that chemotherapy induces ECM remodeling and subsequently type XVII ectodomain shedding that would initiate the proliferation of dormant cancer cells. Here, COL17A1 is linked to colorectal carcinoma.