The role of a Golgi-specific protein PAQR3 in epithelial-mesenchymal transition mediated by WNT2B in gastric cancer
【摘要】：It remains elusive whether deregulated WNT2 B pathway is involved in EMT, an early event that occurs during metastasis of gastric cancers(GC). Here, we demonstrated that WNT2 B induced GC cells to undergo a transition from the epithelial to the spindle-like mesenchymal morphology. WNT2 B reduced Ecadherin expression and increased that of mesenchymal proteins. In search of a downstream mediator that may account for WNT2 B-induced EMT, we focused on transcription repressors of E-cadherin, TWIST, SLUG, and Snail and found that cancer cells express high levels of TWIST and that PAQR3 downexpression enhances TWIST expression. PAQR3 downexpression significantly increases TWIST transcripts and protein in WNT2 B-expressing lines. Forced expression of PAQR3 can lower the expression of TWIST expression in WNT2 B expression cells. TWIST expression is suppressed by PAQR3. CHIP assays and western blot further showed that PAQR3 can promote the degradation of TWIST protein by regulated the ubiquitin proteasome pathway(UPP). Together, we reported here that WNT2 B signaling pathways induce EMT in gastric cancer cells via TWIST gene expression by PAQR3 loss.