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

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

Research output: Contribution to journalArticle

138 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1324-1332
Number of pages9
JournalOncogene
Volume22
Issue number9
DOIs
StatePublished - Mar 6 2003

Keywords

  • Breast cancer
  • C-src
  • Invasion
  • MUC1
  • erbB
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Schroeder, J. A., Adriance, M. C., Thompson, M. C., Camenisch, T. D., & Gendler, S. J. (2003). MUC1 alters β-catenin-dependent tumor formation and promotes cellular invasion. Oncogene, 22(9), 1324-1332. https://doi.org/10.1038/sj.onc.1206291