A wide variety of signaling transduction pathways contribute to tumorigenesis. Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family and its upregulation is closely correlated with tumor progression and prognosis of multiple cancer types, including colorectal cancer. However, the molecular mechanisms by which FOXQ1 promotes tumorigenesis, especially cancer cell invasion and metastasis in colorectal cancer, have not been fully elucidated. In the present study, we demonstrate that FOXQ1 is overexpressed in colorectal tumor tissues and its expression level is closely correlated with the stage and lymph node metastasis of colorectal cancer. In in vitro cultured SW480 colorectal cancer cells, knockdown of FOXQ1 expression by small interfering RNA greatly diminished the aggressive tumor behaviors of SW480 cells, including angiogenesis, invasion, epithelial-mesenchymal transition, and resistance to chemotherapy drug-induced apoptosis. Further mechanistic investigation showed that FOXQ1 silencing prevents the nuclear translocation of β-catenin, thus reducing the activity of Wnt signaling. Moreover, TGF-β1 induced the expression of FOXQ1 as well as the migration and invasion of SW480 cells, which was partially prevented following knockdown of FOXQ1. Our results demonstrate that FOXQ1 plays a critical role during the tumorigenesis of colorectal cancer and is a mediator of the crosstalk between Wnt and TGF-β signaling pathways. Our findings provide further insight into the cancer biology of colorectal cancer and suggest that FOXQ1 is a potential therapeutic target for the development of therapies for colorectal cancer.
Keywords: 5-FU, 5-fluorouracil; 7-AAD, 7-aminoactinomycin D; DAPI, 4′,6-diamidino-2-phenylindole; DEPC, Diethy pyrocarbonate; DMSO, Dimethyl sulfoxide; EMT, Epithelial-Mesenchymal transition; FOXQ1; FOXQ1, Forkhead Box Q1; L-OHP, Oxaliplatin; MMP2, Matrix metalloproteinase-2; MiRNA, MicroRNA; NC-shRNA, Negative Control-shRNA; PBS, Phosphate buffer solution; PBS, phosphate buffered saline; PKA, proteinkinase A; PVDF, Polyvinylidene fluoride; RNAi, RNA interference; SDS, Sodium dodecyl sulfonate; TBS, Tris-buffered saline; TEMED, Tetra methyl ethylene diamine; TGF-β, Transformin growth β; TGF-β1; Tris, Trihydroxymethyl minomethane; VEGF-A, Vascular endothelial growth factor-A; Wnt signaling; aggressive tumor behavior; cDNA, Complementary DNA; colorectal cancer; ddH2O, double distilled H2O; epithelial-mesenchymal transition; qRT-PCR, Quantitative real-time PCR; shRNA, Short hairpin RNA; μg, Microgramme; μl, Microliter.