Fig. 5

KITENIN promotes the downregulation of transcriptional regulators involved in aerobic glycolysis and of nuclear PKM2, β-catenin, and HIF-1α. To determine whether KITENIN overexpression or knockdown affects the expression of downstream effectors, their expression was analyzed using qRT-PCR and Western blotting. A–C mRNA expression and protein level of β-catenin, c-Myc, cyclin D1, and CD44 in CaCo2/EV and CaCo2/KITENIN cells. D–F KITENIN knockdown reduces the mRNA expression and protein level of β-catenin, c-Myc, cyclin D1, and CD44 in CaCo2/EV cells. G mRNA expression of HIF-1α in CaCo2/EV and CaCo2/KITENIN cells and H HIF-1α mRNA expression in KITENIN-silenced cells. I–J KITENIN increases HIF-1α protein level under both normoxic and hypoxic conditions in CaCo2/EV and CaCo2/KITENIN cells. K The GEPIA web tool was used to analyze the relationship of the mRNA expression of KITENIN with that of β-catenin, c-Myc, CD44, cyclin D1, and HIF-1α in COAD samples. L Overall survival curve of between KITENIN-β-catenin, KITENIN-MYC, KITENIN-CD44, KITENIN-CyclinD1, and KITENIN-HIF-1α levels, according to the GEPIA database. M Schematic illustration of how KITENIN increases nuclear PKM2, and PKM2 binds to β-catenin and HIF-1α, creating a feedback loop between c-Myc, PKM2, and HIF-1α. N KITENIN increases the nuclear localization of β-catenin, HIF-1α, and PKM2 in CaCo2/EV cells. Lamin B was used as a nuclear marker. O Nuclear-to-cytoplasmic ratios of β-catenin, HIF-1α, and PKM2 in CaCo2/EV and CaCo2/KITENIN cells. Data are the mean ± standard deviation, n = 3 * p < 0.05; ** p < 0.01; *** p < 0.001, NS, no significant difference between groups