A meta-analyses on the role of IL-6 associated JAK/STAT3 signaling pathway modulation in the inflammatory bowel disease complicated colonic cancer development

Year 2021, Volume: 3 Issue: Supplement 1, 4 - 6, 07.03.2021

Ece Ünal Çetin , Yavuz Beyazıt

https://doi.org/10.46310/tjim.875560

Abstract

The signalling pathway of Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) is suggested to be involved in various pathophysiological processes, including immune function, cell growth, differentiation, hematopoiesis and more importantly oncogenesis of distinct tumoral conditions. Interleukin (IL) 6 is a proinflammatory cytokine produced by antigen-presenting cells and non-hematopoietic cells in response to external stimuli and considered to be a key player in the development of the microenvironment of malignancy by promoting tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue. Recent studies suggest that aberrant interleukin IL6/JAK/STAT3 signaling pathway exists in both IBD and inflammation-related gastrointestinal cancers. In the present meta-analysis we aimed to analyze the relationship between IL-6/JAK/STAT3 and IBD associated colorectal carcinogenesis and the effect of the inhibition of this system on disease follow-up and management.In light of the small number of studies able to be included in the meta-analysis evidence strongly proposed that JAK/STAT3 signaling, especially via the IL-6/STAT3 axis is involved in the transition of inflammatory lesions to tumoral diseases and leading to ulcerative colitis associated colorectal cancer. For this reason, based on the evidence presented in this meta-analysis it is reasonable to suggest that targeting components of the IL-6/JAK/STAT3 signalling pathway can inhibit tumour cell growth and relieve immunosuppression in the UC associated colonic tumoral microenvironment.

Keywords

inflammatory bowel disease, colon cancer, IL-6, JAK/STAT3

References

• Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell. 2009;15(2):103-13.
• Li Y, de Haar C, Chen M, Deuring J, Gerrits MM, Smits R et al. Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis. Gut. 2010;59(2):227-35.
• Yang X, Zhang F, Wang Y, Cai M, Wang Q, Guo Q et al. Oroxylin A inhibits colitis-associated carcinogenesis through modulating the IL-6/STAT3 signaling pathway. Inflamm Bowel Dis. 2013;19(9):1990-2000.
• Chakilam S, Gandesiri M, Rau TT, Agaimy A, Vijayalakshmi M, Ivanovska J et al. Death-associated protein kinase controls STAT3 activity in intestinal epithelial cells. Am J Pathol. 2013;182(3):1005-20.
• Kim SW, Park KC, Jeon SM, Ohn TB, Kim TI, Kim WH et al. Abrogation of galectin-4 expression promotes tumorigenesis in colorectal cancer. Cell Oncol (Dordr). 2013;36(2):169-78.
• Dai Y, Jiao H, Teng G, Wang W, Zhang R, Wang Y et al. Embelin reduces colitis-associated tumorigenesis through limiting IL-6/STAT3 signaling. Mol Cancer Ther. 2014;13(5):1206-16.
• Saadatdoust Z, Pandurangan AK, Ananda Sadagopan SK, Mohd Esa N, Ismail A, Mustafa MR. Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL-6/STAT3 pathway. J Nutr Biochem. 2015;26(12):1547-58.
• Chen YY, Ma ZB, Xu HY, Shi LJ, Li DY, Sun LY et al. IL-6/STAT3/SOCS3 signaling pathway playing a regulatory role in ulcerative colitis carcinogenesis. Int J Clin Exp Med. 2015;8(8):12009-17.
• Do EJ, Hwang SW, Kim SY, Ryu YM, Cho EA, Chung EJ et al. Suppression of colitis-associated carcinogenesis through modulation of IL-6/STAT3 pathway by balsalazide and VSL#3. J Gastroenterol Hepatol. 2016;31(8):1453-61.
• Zhang S, Li J, Xie P, Zang T, Shen H, Cao G et al. STAT3/c-Myc Axis-Mediated Metabolism Alternations of Inflammation-Related Glycolysis Involve with Colorectal Carcinogenesis. Rejuvenation Res. 2019;22(2):138-145.
• Ye X, Wu H, Sheng L, Liu YX, Ye F, Wang M et al. Oncogenic potential of truncated RXRα during colitis-associated colorectal tumorigenesis by promoting IL-6-STAT3 signaling. Nat Commun. 2019;10(1):1463.
• Huangfu S, Dou R, Zhong S, Guo M, Gu C, Jurczyszyn A et al. Modified Pulsatillae decoction inhibits DSS-induced ulcerative colitis in vitro and in vivo via IL-6/STAT3 pathway. BMC Complement Med Ther. 2020;20(1):179.