MUCI, a tumor associated glycoprotein, is over-expressed in most cancers and can promote proliferation and metastasis. The objective of this research was to study the role of MUCI in cancer metastasis and its potential mechanism. Pancreatic (PANCI) and breast (MCF-7) cancer cells with stable 'knockdown' of MUCI expression were created using RNA interference. P-Catenin and E-cadherin protein expression were upregulated in PANCI and MCF-7 cells with decreased MUCI expression. Downregulation of MUCI expression also induced beta-catenin relocation from the nucleus to the cytoplasm, increased E-cadherin/beta-catenin complex formation and E-cadherin membrane localization in PANCI cells. PANCI cells with 'knockdown' MUCI expression had decreased in vitro cell invasion. This study suggested that MUCI may affect cancer cell migration by increasing E-cadherin/beta-catenin complex formation and restoring E-cadherin membrane localization. (c) 2007 Elsevier Inc. All rights reserved.