title: Loss of E-cadherin and epithelial to mesenchymal transition is not required for cell motility in tissues or for metastasis.
abstract: Loss of E-cadherin has been long considered to be a major hallmark of epithelial-mesenchymal transition (EMT) and has been reported in various cancers. P120 catenin regulates E-cadherin stability on the cell surface and also plays a role in intracellular signaling by modulating nuclear transcription. We recently characterized the nature of interactions between p120 catenin and Mucin 1 (MUC1) in pancreatic cancer. Expression of different p120 catenin isoforms with and without MUC1 induced distinct morphologies, cell adhesion, and dynamic properties of motility along with different metastatic properties in vivo. Re-expression of p120 catenin isoform 3A in the context of MUC1 expression in a p120 catenin-deficient cell line stabilized expression of E-cadherin. However, orthotopic implantation of tumors using this stable cell line produced large metastatic lesions to the liver, which exceeded the volume of the primary tumor, suggesting down regulation of E-cadherin is not required for tumor metastasis. Here we extend those studies by showing that ectopic expression of E-cadherin does not block in vitro invasion of the pancreatic cancer cells, and instead accelerated the rate of tumor invasion. Furthermore, results from 23 cases of human pancreatic primary tumor specimens revealed that most tumors exhibiting metastatic activity retained epithelial morphology and E-cadherin gene expression. Our results indicate that loss of E-cadherin and EMT are not required for metastasis and that an epithelial morphology can be maintained during the process of tumor cell movement.
authors.affiliation: Department of Cancer Biology; Mayo Clinic Comprehensive Cancer Center; Mayo Clinic ; Jacksonville, FL USA ; Eppley Institute For Research in Cancer and Allied Disease; University of Nebraska Medical Center ; Omaha, NE USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biochemisty and Molecular Biology; University of Nebraska Medical Center ; Omaha, NE USA.
authors.forename: Huocong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of General Surgery; Veterans Administration; University of Nebraska Medical Center ; Omaha, NE USA.
authors.forename: Neeley
authors.initials: N
authors.lastname: Remmers
authors.affiliation: Eppley Institute For Research in Cancer and Allied Disease; University of Nebraska Medical Center ; Omaha, NE USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
keywords: E-cadherin; EMT, epithelial to mesenchymal transition; Epithelial to Mesenchymal Transition; MUC1; Mucin 1, MUC1; P120 catenin; Pancreatic cancer metastasis; cell motility; ctn, catenin