title: Dynamic activation of the key pathways: linking colitis to colorectal cancer in a mouse model.
abstract: An association between carcinogenesis and inflammation has long been appreciated. Chemically induced colitis-associated cancer (CAC) is a classical mouse model for investigating 'inflammation-cancer link' in the intestine. Diverse mechanisms behind this non-resolving inflammation model have been reported before, most of them were emphasized on key cancer genes, cytokines, and signal transduction abnormality based on prior knowledge. In this study, we dynamically and globally dissect the alteration of key pathways in the development from colitis to colorectal cancer. Striking evidence from gene expression profiling, serum cytokines detection, and immunohistochemistry analysis all reveals that different key pathways [NF-κB, STAT3, p38 mitogen-activated protein kinase (MAPK), and Wnt/β-catenin signaling] and their target genes are hyperactive in different phases of the inflammation-cancer link. Nuclear factor-κB (NF-κB) and STAT3 signaling are hyperactive in the whole process, while p38 MAPK and Wnt/β-catenin signaling are only hyperactive in the beginning and ending, respectively. Through this unbiased system biological approach, we provide strong evidence that different key pathways are specifically involved in different phases, which bridge the gap between inflammation and cancer.
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital of Central South University Changsha, Hunan, China.
authors.forename: Anliu
authors.initials: A
authors.lastname: Tang
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Liyang
authors.initials: L
authors.lastname: Zhang
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Shourong
authors.initials: S
authors.lastname: Shen
mesh_terms: D000818:Animals; D003092:Colitis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D048051:p38 Mitogen-Activated Protein Kinases