Biology subjects

Bu, X.

Publications and source records attributed to Bu, X..

2 recordsLinked to original sources

bioRxiv2018

Migration of gastric cancer is suppressed by rabies virus glycoprotein via regulating α7-nicotinic acetylcholine receptors/ERK-EMT

Nicotinic acetylcholine receptors (nAChRs) have been reported to be overexpressed in malignancies in humans and is associated with tumorigenesis and cell migration. In previous studies of gastric cancer, alpha7 nicotinic acetylcholine receptor (7-nAChR) overexpression can induce epithelial-mesenchymal transition (EMT) and promote migration of gastric cancer cells. Recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing the rabies virus glycoprotein (rL-RVG) may promote apoptosis of gastric cancer cells and reduces migration of lung cancer metastasis. However, whether rL-RVG inhibits migration of gastric cancer cells and what the underlying functional mechanism is remains unknown. In this study, our findings demonstrate that rL-RVG suppressed migration and reduced EMT of gastric cancer cells via 7-nAChR in vitro. Furthermore rL-RVG decreased the phosphorylation levels of the MEK/ERK signaling pathway such as down-regulating the expression of P-MEK and P-ERK. Additionally, rL-RVG also reduced the expression level of mesenchymal markers N-cadherin and Vimentin and enhanced the expression of the epithelial marker E-cadherin. Lastly, rL-RVG together with nicotinic acetylcholine receptors (nAChRs) inhibited gastric cancer epithelial to mesenchymal transition (EMT) which suppressed gastric cancer cell migration. We also found that rL-RVG suppresses the growth of gastric cancer subcutaneous tumor cells in vivo. Thus, rL-RVG inhibits 7-nAChR-MEK/ERK-EMT to suppress migration of gastric cancer cells.

cancer biology↗

bioRxiv2018

NDRG2 Regulates Adherens Junction Integrity to Restrict Colitis and Tumorigenesis

Paracellular barriers play an important role in the pathogenesis of IBDs and maintain gut homeostasis. N-myc downstream-regulated gene 2 (NDRG2) has been reported to be a tumor suppressor gene and inhibits colorectal cancer metastasis. However, whether NDRG2 affects colitis initiation and colitis-associated colorectal cancer is unclear. Here, We found that intestine-specific Ndrg2 deficiency caused mild spontaneous colitis with ageing, aggravated DSS and TNBS induced colitis, increased AOM-DSS induced colitis-associated tumor. Ndrg2 loss led to adherens junction (AJ) structure destruction via E-cadherin expression attenuation, resulting in diminished epithelial barrier function and increased intestinal epithelial permeability. Mechanistically, NDRG2 enhancing the interaction of E3 ligase FBXO11 with Snail, the repressor of E-cadherin, to promote Snail degradation by ubiquitination, and maintained E-cadherin expression. In human ulcerative colitis patients, reduced NDRG2 expression is positively correlated with severe inflammation. These findings demonstrate that NDRG2 is an essential colonic epithelial barrier regulator and plays important role in gut homeostasis maintenance and colitis-associated tumor development. SUMMARYAdherens junctoin (AJ) as the key part of intestinal epithelial barrier plays important role in the pathogenesis of IBDs. Intestinal specific Ndrg2 loss attenuates E-cadherin expression and disrupts the integrity of AJ structure which is feasible for colitis and tumor development.

cancer biology↗