THE INTERACTIONS OF APC, E-CADHERIN AND BETA-CATENIN IN TUMOR-DEVELOPMENT AND PROGRESSION

Much progress has been made in identifying genes mutated during the de velopment of colorectal carcinoma. Mutation of the APC gene in particu lar appears to be fundamental for colorectal tumour initiation. In con trast, loss of expression of E-cadherin appears to be a late event, wh ich may be important in the development of invasion. Recent clarificat ion of the function of APC, however, has shown that it exists in equil ibrium with beta-catenin and E-cadherin. This review discusses the fun ctions of these molecules, their interactions, and how APC mutations m ay alter the equilibrium with beta-catenin and E-cadherin. It is argue d that these changes cause aberrant architectural development of tissu e, which results in loss of growth control. It is this escape from gro wth control, rather than acquisition of cell-autonomous growth which r esults in the initial development of adenomas. The role of the E-cadhe rin-catenin unit in colorectal tumour invasion is discussed and the ev idence is reviewed for the involvement of APC and E-cadherin in tumour s arising from non-intestinal epithelia. (C) 1997 by John Wiley & Sons , Ltd.