Cancer Res 2014 Mar 26;74(5):1609-20. Epub 2013 Dec 26.
Authors' Affiliations: Eppley Institute for Research in Cancer and Allied Disease; Department of Oral Biology, University of Nebraska Medical Center, Omaha, Nebraska; Department of Gynecologic Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Translational Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California.
The mechanisms by which MUC1 and p120 catenin contribute to progression of cancers from early transformation to metastasis are poorly understood. Here we show that p120 catenin ARM domains 1, 3-5, and 8 mediate interactions between p120 catenin and MUC1, and that these interactions modulate dynamic properties of cell adhesion, motility, and metastasis of pancreatic cancer cells. We also show that different isoforms of p120 catenin, when coexpressed with MUC1, create cells that exhibit distinct patterns of motility in culture (motility independent of cell adhesion, motility within a monolayer while exchanging contacts with other cells, and unified motility while maintaining static epithelial contacts) and patterns of metastasis. The results provide new insight into the dynamic interplay between cell adhesion and motility and the relationship of these to the metastatic process.