NF-kappaB signaling pathway, inflammation and colorectal cancer.
There is growing evidence for a connection between inflammation and tumor development, and the nuclear factor kappa B (NF-kappaB), a proinflammatory transcription factor, is hypothesized to promote tumorigenesis. Although the genetic evidence for the hypothesis has been lacking, recent papers have lent credence to this hypothesis. It has been reported that constitutive NF-kappaB activation in inflammatory bowel diseases (IBDs) increases risk of colorectal cancer (CRC) in the patients with the number of years of active disease. NF-kappaB activation might induce cellular transformation, mediate cellular proliferation, prevent the elimination of pre-neoplastic and fully malignant cells by up-regulating the anti-apoptosis proteins. Furthermore, NF-kappaB may contribute to the progression of CRC by regulating the expression of diverse target genes that are involved in cell proliferation (Cyclin D1), angiogenesis (VEGF, IL-8, COX2), and metastasis (MMP9). These findings implicate NF-kappaB inhibition as an important therapeutic target in CRC. However, due to lack of knowledge about the specific roles of different NF-kappaB subunits in different stage of carcinogenesis, and compounds to block specific subunits of NF-kappaB family, it will be a long time before the coming of targeting NF-kappaB in CRC therapy.
Wang
Soly
S
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Liu
Zhanjie
Z
Wang
Lunshan
L
Zhang
Xiaoren
X
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000150:complications; D015212:Inflammatory Bowel Diseases / Q000150:complications; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D021122:Protein Subunits