TIGAR is required for efficient intestinal regeneration and tumorigenesis

Cheung, E.C., Athineos, D., Lee, P., Ridgway, R.A., Lambie, W., Nixon, C., Strathdee, D., Blyth, K., Sansom, O.J. and Vousden, K.H. (2013) TIGAR is required for efficient intestinal regeneration and tumorigenesis. Developmental Cell, 25(5), pp. 463-477. (doi:10.1016/j.devcel.2013.05.001)

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Abstract

Regulation of metabolic pathways plays an important role in controlling cell growth, proliferation, and survival. TIGAR acts as a fructose-2,6-bisphosphatase, potentially promoting the pentose phosphate pathway to produce NADPH for antioxidant function and ribose-5-phosphate for nucleotide synthesis. The functions of TIGAR were dispensable for normal growth and development in mice but played a key role in allowing intestinal regeneration in vivo and in ex vivo cultures, where growth defects due to lack of TIGAR were rescued by ROS scavengers and nucleosides. In a mouse intestinal adenoma model, TIGAR deficiency decreased tumor burden and increased survival, while elevated expression of TIGAR in human colon tumors suggested that deregulated TIGAR supports cancer progression. Our study demonstrates the importance of TIGAR in regulating metabolism for regeneration and cancer development and identifies TIGAR as a potential therapeutic target in diseases such as ulcerative colitis and intestinal cancer.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nixon, Mr Colin and Blyth, Dr Karen and Vousden, Karen and Cheung, Mr Eric and Strathdee, Dr Douglas and Ridgway, Dr Rachel and Lambie, Mrs Wendy and Sansom, Professor Owen
Authors: Cheung, E.C., Athineos, D., Lee, P., Ridgway, R.A., Lambie, W., Nixon, C., Strathdee, D., Blyth, K., Sansom, O.J., and Vousden, K.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Developmental Cell
ISSN:1534-5807
ISSN (Online):1878-1551

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