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MUC1 alters β-catenin-dependent tumor formation and promotes cellular invasion

Oncogene volume 22, pages 1324–1332 (2003)Cite this article

Abstract

MUC1 is aberrantly expressed in greater than 90% of all breast carcinomas, yet its function as a tumor antigen is not fully understood. Recently, studies have shown that MUC1 interacts with β-catenin, erbB receptors, src, GSK-3β and protein kinase Cδ, possibly in a complex that promotes the disassembly of adherens junctions and the invasion of cells. Here we show that the deletion of Muc1 expression from MMTV-Wnt-1 transgenic mice results in a significant increase in the time to mammary gland tumor onset. Analysis of MMTV-Wnt-1 tumors on a wild-type Muc1 background shows a tumor-specific complex formation between Muc1 and β-catenin that can be observed in both the membrane and the cytoplasm of transformed epithelium. Analysis of primary human adenocarcinomas revealed that this MUC1/β–catenin interaction occurs in both primary and metastatic tumors, but is dramatically increased in metastatic lesions. Addition of MUC1-cytoplasmic domain peptides to the invasive MDA-MB-468 and MDA-MB-231 cell lines increases their invasive capability, and these peptides colocalize with both β-catenin and the focal adhesion protein vinculin, primarily at sites of membrane invasion into a collagen matrix. These data indicate a potential mechanism for MUC1 promotion of invasive tumorigenesis in the breast through the modulation of β-catenin localization and subsequent cytoskeletal dynamics.

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Acknowledgements

This study was supported by grants from the NIH, CA64389 (to SJG), CA81703 (to JAS) and CA90204 (to MCA). We are grateful to Dr Robert Cardiff (University of California – Davis, Davis, CA, USA) for pathological analysis of mouse tissues. We thank Marvin H Ruona for computer graphics, Jose Luis for statistical analysis and the Mayo Clinic Hospital Surgical Pathologists for human tissue procurement and pathological analysis and Carol Williams for administrative assistance.

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  1. Tumor Biology Program and Department of Biochemistry and Molecular Biology, Mayo Medical/Graduate School, Mayo Clinic Scottsdale, Scottsdale, 85259, AZ, USA

    Joyce A Schroeder, Melissa C Adriance, Melissa C Thompson, Todd D Camenisch & Sandra J Gendler

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  1. Joyce A Schroeder
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  2. Melissa C Adriance
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  3. Melissa C Thompson
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Correspondence to Sandra J Gendler.

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Schroeder, J., Adriance, M., Thompson, M. et al. MUC1 alters β-catenin-dependent tumor formation and promotes cellular invasion. Oncogene 22, 1324–1332 (2003). https://doi.org/10.1038/sj.onc.1206291

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