Goosecoid drives colorectal cancer progression by inducing epithelial-mesenchymal transition

BACKGROUND Colorectal cancer (CRC) poses a substantial public health burden worldwide, consistently exhibiting a notable incidence among malignancies across the globe. Goosecoid (GSC), an evolutionarily conserved homeodomain transcription factor, is recognized as a pivotal organizer gene during embryonic development and has been increasingly associated with oncogenic processes. Despite its established roles in other cancers, the specific functions and molecular mechanisms of GSC in the pathogenesis of CRC remain to be fully elucidated. This study therefore aimed to investigate the contribution of GSC to CRC progression and elucidate the underlying mechanistic pathways. AIM To investigate the oncogenic properties of GSC and elucidate its mechanism of action in CRC. METHODS We validated the expression levels of GSC in CRC tissues using the UALCAN database, Western blotting, immunohistochemistry, and immunofluorescence. The association between GSC and CRC prognosis was analyzed via the Kaplan-Meier Plotter database. The effects of GSC on CRC proliferation, invasion, and metastasis were systematically evaluated through a set of functional assays, such as colony formation assay, Transwell migration and invasion assay, wound healing assay, and tube formation assay. RESULTS Through the UALCAN database, Kaplan-Meier Plotter database, western blotting, immunohistochemistry, and immunofluorescence, we found that GSC was significantly upregulated in CRC. High expression of GSC in CRC was associated with poorer recurrence-free survival and overall survival. Furthermore, in vitro studies showed that knocking down GSC inhibited the epithelial-mesenchymal transition (EMT) process, proliferation, invasion, and metastasis of CRC cells; conversely, overexpression of GSC significantly enhanced the EMT process, proliferation, invasion, and metastasis of CRC cells. Mechanistically, we found that knockdown and overexpression of GSC altered the abundance of target proteins linked to the Wnt/β-catenin signaling cascade. CONCLUSION By activating the Wnt/β-catenin signaling axis, GSC drives CRC progression and EMT, positioning it as a viable diagnostic and therapeutic target.