| First Author | Wang L | Year | 2016 |
| Journal | Inflamm Bowel Dis | Volume | 22 |
| Issue | 5 | Pages | 1107-18 |
| PubMed ID | 26891257 | Mgi Jnum | J:320214 |
| Mgi Id | MGI:6868934 | Doi | 10.1097/MIB.0000000000000729 |
| Citation | Wang L, et al. (2016) PDCD4 Deficiency Aggravated Colitis and Colitis-associated Colorectal Cancer Via Promoting IL-6/STAT3 Pathway in Mice. Inflamm Bowel Dis 22(5):1107-18 |
| abstractText | BACKGROUND: Although programmed cell death (PDCD) 4 is generally considered to be a new tumor suppressor, the consequence of Pdcd4 deficiency in tumorigenesis is not well established. The role of PDCD4 in colitis-associated colorectal carcinoma (CRC) remains unknown. METHODS: Experimental colitis and CRC were induced by dextran sodium sulfate and dextran sodium sulfate with azoxymethane, respectively, in wild type and Pdcd4 knockout (Pdcd4(-/-)) mice and were evaluated by clinical examination and histopathology. Levels of cytokines were detected by enzyme-linked immunosorbent assay. Changes in signaling pathways were examined by Western blot and immunofluorescent staining. Cell proliferation was determined by BrdU incorporation and Cell Counting Kit-8 staining. RESULTS: Pdcd4 deficiency not only aggravated the dextran sodium sulfate-induced acute colitis but also promoted the development of colitis-induced CRC. Mechanically, Pdcd4 deficiency accelerated epithelial cell proliferation during tumorigenesis, markedly up-regulated the expression of proinflammatory cytokines, such as interleukin (IL)-6, and enhanced the activation of signal transducer and activator of transcription (STAT3), a IL-6 downstream effector. Using purified cells, we found that Pdcd4 deficiency increased IL-6 expression in vitro and the susceptibility to IL-6/STAT3 pathway-mediated cell proliferation significantly. Furthermore, blockade of IL-6/STAT3 pathway through sgp130Fc reversed the promoting effect of Pdcd4 deficiency on colonic epithelial cell proliferation in vivo. CONCLUSION: The Pdcd4 deficiency accelerates colitis and colitis-associated CRC presumably through up-regulating IL-6/STAT3 pathway, suggesting that PDCD4 plays a protective role in inflammation-associated carcinoma and might be a potential target for the treatment of CRC. |
