Knockdown of LRCH4 Remodels Tumor Microenvironment Through Inhibiting YAP and TGF-ß/Smad Signaling Pathway in Colorectal Cancer.

ABSTRACT

BACKGROUND: Colorectal cancer is one of the most common gastrointestinal malignancies worldwide. LRCH4 is the top 1 gene associated with an unfavorable prognosis in colorectal cancer. METHODS: Here, we reported that the knockdown of LRCH4 inhibited the proliferation, migration and invasion in HT29 cells. RESULTS: The activity of Yes-Associated Protein (YAP), a transcription factor in the Hppo-YAP signaling pathway, was significantly inhibited by LRCH4-siRNA. LRCH4 knockdown also reversed the EMT and regulated the expression of extracellular matrix (ECM) protein, Fibronectin and Collagen IV in HT29 cells. In addition, the TGF-ß/Smad signaling pathway, as the downstream pathway of Yap, was also inhibited by LRCH4 knockdown. CONCLUSION: Knockdown of LRCH4 involved in the regulation of ECM and EMT and inhibited YAP and the TGF-ß/Smad signaling pathway in colorectal cancer cells. Our study provided a mechanism of LRCH4 on colorectal cancer cells, and a new potential target for clinical tumor treatment.