A causal role for E-cadherin in the transition from adenoma to carcinoma

AK Perl, P Wilgenbus, U Dahl, H Semb, G Christofori - Nature, 1998 - nature.com
AK Perl, P Wilgenbus, U Dahl, H Semb, G Christofori
Nature, 1998nature.com
Abstract Development of malignant tumours is in part characterized by the ability of a tumour
cell to overcome cell–cell adhesion and to invade surrounding tissue. E-cadherin is the main
adhesion molecule of epithelia,, and it has been implicated in carcinogenesis because it is
frequently lost in human epithelial cancers,,. Re-establishing the functional cadherin
complex in tumour cell lines results in a reversion from an invasive to a benign epithelial
phenotype. However, it remained unresolved whether the loss of E-cadherin-mediated cell …
Abstract
Development of malignant tumours is in part characterized by the ability of a tumour cell to overcome cell–cell adhesion and to invade surrounding tissue. E-cadherin is the main adhesion molecule of epithelia,, and it has been implicated in carcinogenesis because it is frequently lost in human epithelial cancers,,. Re-establishing the functional cadherin complex in tumour cell lines results in a reversion from an invasive to a benign epithelial phenotype. However, it remained unresolved whether the loss of E-cadherin-mediated cell adhesion was a cause or a consequence of tumour progression in vivo. Here we report that the loss of E-cadherin expression coincides with the transition from well differentiated adenoma to invasive carcinoma in a transgenic mouse model of pancreatic β-cell carcinogenesis (Rip1Tag2). Intercrossing Rip1Tag2 mice with transgenic mice that maintain E-cadherin expression in β-tumour cells results in arrest of tumour development at the adenoma stage, whereas expression of a dominant-negative form of E-cadherin induces early invasion and metastasis. The results demonstrate that loss of E-cadherin-mediated cell adhesion is one rate-limiting step in the progression from adenoma to carcinoma.
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