Lipopolysaccharide-induced α-catenin downregulation enhances the motility of human colorectal cancer cells in an NF-κB signaling-dependent manner

Abstract

α-Catenin is an important molecule involved in the maintenance of cell–cell adhesion and a prognostic marker in cancer since its expression is essential for preventing cancer metastasis. However, the mechanism that leads to the downregulation of α-catenin in cancer progression remains unclear. The present study revealed that lipopolysaccharide (LPS)-induced NF-κB signaling activation suppressed α-catenin expression and motility in SW620 colorectal cancer (CRC) cells, using real-time polymerase chain reaction, Western blotting, and transwell migration assays. LPS treatment reduced both the mRNA and protein expression of α-catenin and thereby enhanced cell motility. Conversely, incubating cells with an NF-κB inhibitor disrupted these effects. Furthermore, the ectopic expression of p65 alone mimicked the effects of LPS stimulation. In CRC tissues, the presence of enteric bacterial LPS-related neutrophil-enriched foci was correlated with α-catenin downregulation. Collectively, these findings suggest that LPS-induced NF-κB signaling is related to α-catenin suppression and enhanced cell motility in CRC. Therefore, NF-κB is a novel potential therapeutic target for CRC metastasis.

Lipopolysaccharide (LPS) enhances prostate cancer metastasis potentially through NF‐κB activation and recurrent dexamethasone administration fails to suppress it in vivo

“…Despite certain unexpected results, our in vivo study has for the first‐time provided the evidence that systemic administration of LPS could activate NF‐κB in PCa cells (Figures A and B) and enhance PCa cells metastasis in a cell line dependent manner (Figure A). We believe that, this effect could be through both direct and indirect methods of LPS‐mediated NF‐κB activation in PCa cells . No metastasis was observed in our DU145 orthotopic tumor model that confirms previously reported less metastatic nature of these cells .…”

“…However, migration assay carried out with LPS‐induced secretory factors (10% plasma) as a chemo‐attractant (lower chamber) indicates that the remarkable increase in the migration of cells might be due to the strong chemo‐attractant properties of LPS‐induced factors (Figure C). The aforementioned, in vitro experiments also supported various other studies that show pro‐migratory properties of LPS on cancer cells . However, in the subsequent experiments, our in vivo data reminded us the commonly known fact that in vitro results might not be always recapitulated in vivo.…”

“…Later, several studies showed that endotoxin could promote cancer by enhancing growth, survival, chemoresistance, and metastasis . With reference to metastasis, studies have demonstrated that the LPS induced TLR4 activation in different cancer cells leads to activation of NF‐κB, JNK, MAPK signaling, which further enhance their migration and invasion properties . LPS and LPS‐induced inflammatory cytokines are known to increase the permeability of blood vessels, enhance the expression of adhesion molecules on the cancer cells and endothelial cells which ultimately supports cancer cells extravasation .…”

“…[14][15][16] With reference to metastasis, studies have demonstrated that the LPS induced TLR4 activation in different cancer cells leads to activation of NF-κB, JNK, MAPK signaling, which further enhance their migration and invasion properties. 17,18 LPS and LPS-induced inflammatory cytokines are known to increase the permeability of blood vessels, enhance the expression of adhesion molecules on the cancer cells and endothelial cells which ultimately supports cancer cells extravasation. 14,19 LPS-mediated local inflammation and/or tissue damage in organs like lung favours metastasis to these sites.…”

Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

“…The combination of ibuprofen plus LPS was tested in colorectal cancer patients and showed encouraging results. But recently it has been shown that LPS enhance the motility in CRC cells by mediating NF‐κB signaling and α‐catenin suppression (Cheng et al, ).…”