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The links between axin and carcinogenesis

Ontario Cancer Institute, Division of Experimental Therapeutics, Toronto, Ontario, Canada, M5G 2M9

Correspondence to:
Dr S Salahshor
Ontario Cancer Institute, Division of Experimental Therapeutics, 610 University Ave, M5G 2M9, Toronto, ON, Canada; Salahsho{at}Uhnres.Utoronto.Ca
ABSTRACT
The products of the two mammalian Axin genes (Axin1 and its homologue Axin2) are essential for the degradation of ß catenin, a component of Wnt signalling that is frequently dysregulated in cancer cells. Axin is a multidomain scaffold protein that has many functions in biological signalling pathways. Overexpression of axin results in axis duplication in mouse embryos. Wnt signalling activity determines dorsal–ventral axis formation in vertebrates, implicating axin as a negative regulator of this signalling pathway. In addition, Wnts modulate pattern formation and the morphogenesis of most organs by influencing and controlling cell proliferation, motility, and fate. Defects in different components of the Wnt signalling pathway promote tumorigenesis and tumour progression. Recent biochemical studies of axins indicate that these molecules are the primary limiting components of this pathway. This review explores the intriguing connections between defects in axin function and human diseases.

Abbreviations: aa, amino acids; AD, Alzheimer’s disease; APC, adenomatous polyposis coli; CKI/II, casein kinase I/II; DIX, Dishevelled and axin binding domain; DVL, Dishevelled; Frat, frequently rearranged in activated T cells; GSK3, glycogen synthase kinase 3; HB, hepatoblastoma; HCC, hepatocellular cancer; JNK, Jun N-terminal kinase; LEF-1, lymphoid enhancer binding factor 1; MB, medulloblastoma; MEKK1, mitogen activated protein/extracellular regulated kinase kinase kinase 1; MID, MEKK binding domain; PP2A, protein phosphatase 2A; RGS, regulator of G protein signalling; SAPK, stress activated protein kinase; SCC, oesophageal squamous cell carcinoma; TCF, T cell specific factor; TGFßR, transforming growth factor ß receptor

Keywords: Axin; Axin1; Axin2; carcinogenesis; colon cancer

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