Mucin 2 silencing promotes colon cancer metastasis through interleukin-6 signaling

Abstract

Downregulation of Mucin 2 (MUC2) expression is associated with early carcinogenesis events in colon cancer. MUC2 plays a role in the progression of colon cancer, and reduced MUC2 protein expression correlates with increased interleukin-6 (IL-6) expression. However, the interaction between MUC2 and IL-6 in colorectal cancer metastasis remains unclear. We systematically analyzed MUC2 and IL-6 expression and determined the survival of cancer patients with high or low MUC2 and IL-6 expression using the Oncomine and PrognoScan databases, respectively. This analysis identified downregulation of MUC2 and overexpression of IL-6 in colon cancer but not in normal colon tissue, and this expression pattern was correlated with poor survival of colon cancer patients. We examined the effects of MUC2 on colon cancer metastasis and used vector-mediated application of short hairpin RNA (shRNA) to suppress MUC2 expression. MUC2 suppressed the migration of colon cancer cells in vitro and dramatically diminished liver metastases in vivo. Treatment with IL-6 increased signal transducer and activator of transcription 3 (STAT3) phosphorylation, promoted checkpoint kinase 2 (Chk2) activation, attenuated cAMP response element-binding protein (CREB) phosphorylation, and suppressed E-cadherin protein expression in MUC2-silenced HT-29 cancer cells. Most importantly, MUC2 is a potential prognostic indicator for colon cancer.

Single-cell derived tumor organoids display diversity in HLA class I peptide presentation

“…5a, b ), whereas we did not detect the proteins in the quantitative proteomics screen. This loss of MUC2 and DACH1 protein expression us not unique to our experimental model, but also broadly observed in CRC 34 – 36 . Along similar lines, HLA peptide ligands from numerous DNA damage sensing proteins (ATR, PRKDC, RAD51) and repair proteins (BCR, BRCA1, BRCA2) were also detected only in CRC organoid lines (Fig.…”

Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

“…Improved metabolic dysfunctions could be explained by the induction of Akkermansia . Furthermore, the changes in gene expression observed in the intestine would support such a hypothesis as transcripts of Muc2 , the predominant secreted mucin from the ileum and colon, were increased ( Velcich et al., 2002 ), and Muc2 deficiency in mice is associated with disruption of epithelial homeostasis and the development of colon cancer ( Hsu et al., 2017 ). In combination, our results suggest that ASP has a major role on the gut microbiome, not only altering the production of metabolites with signaling and energetic functions but also potentially strengthening gut barrier function.…”

Effects of 17beta;-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

“… 41 In addition, Hsu et al . 42 demonstrated MUC2 suppressed the migration of colon cancer cells in vitro and dramatically diminished liver metastasis in vivo through IL-6 signaling. In concordance with these studies, our data also showed that mRNA expression of MUC2 was decreased in AOM/DSS-treated male mice compared to control male mice.…”