00085472can171869-sup-185215_2_supp_4598591_p4fx0l.xlsx (13.52 kB)
Supplemental Table S1 from Tight Junction Protein Claudin-2 Promotes Self-Renewal of Human Colorectal Cancer Stem-like Cells
datasetposted on 2023-03-31, 01:25 authored by Sophie Paquet-Fifield, Shir Lin Koh, Lesley Cheng, Laura M. Beyit, Carolyn Shembrey, Christina Mølck, Corina Behrenbruch, Marina Papin, Meritxell Gironella, Sophie Guelfi, Ramona Nasr, Fanny Grillet, Michel Prudhomme, Jean-Francois Bourgaux, Antoni Castells, Jean-Marc Pascussi, Alexander G. Heriot, Alain Puisieux, Melissa J. Davis, Julie Pannequin, Andrew F. Hill, Erica K. Sloan, Frédéric Hollande
This table contains the sequence of all primers used for qPCR, of siren and shRNAs against claudin-2, as well as details about miRNA mimics and inhibitors used in this work.
National Health and Medical Research Council
ARTICLE ABSTRACTPosttreatment recurrence of colorectal cancer, the third most lethal cancer worldwide, is often driven by a subpopulation of cancer stem cells (CSC). The tight junction (TJ) protein claudin-2 is overexpressed in human colorectal cancer, where it enhances cell proliferation, colony formation, and chemoresistance in vitro. While several of these biological processes are features of the CSC phenotype, a role for claudin-2 in the regulation of these has not been identified. Here, we report that elevated claudin-2 expression in stage II/III colorectal tumors is associated with poor recurrence-free survival following 5-fluorouracil–based chemotherapy, an outcome in which CSCs play an instrumental role. In patient-derived organoids, primary cells, and cell lines, claudin-2 promoted colorectal cancer self-renewal in vitro and in multiple mouse xenograft models. Claudin-2 enhanced self-renewal of ALDHHigh CSCs and increased their proportion in colorectal cancer cell populations, limiting their differentiation and promoting the phenotypic transition of non-CSCs toward the ALDHHigh phenotype. Next-generation sequencing in ALDHHigh cells revealed that claudin-2 regulated expression of nine miRNAs known to control stem cell signaling. Among these, miR-222-3p was instrumental for the regulation of self-renewal by claudin-2, and enhancement of this self-renewal required activation of YAP, most likely upstream from miR-222-3p. Taken together, our results indicate that overexpression of claudin-2 promotes self-renewal within colorectal cancer stem-like cells, suggesting a potential role for this protein as a therapeutic target in colorectal cancer.Significance: Claudin-2-mediated regulation of YAP activity and miR-222-3p expression drives CSC renewal in colorectal cancer, making it a potential target for therapy. Cancer Res; 78(11); 2925–38. ©2018 AACR.