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

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

Research output: Contribution to journalArticle

132 Citations (Scopus)

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

Fingerprint

Catenins
Neoplasms
Breast Neoplasms
Vinculin
Glycogen Synthase Kinase 3
Adherens Junctions
Focal Adhesions
Membranes
Neoplasm Antigens
Human Mammary Glands
Protein Kinase C
Transgenic Mice
Carcinogenesis
Cytoplasm
Adenocarcinoma
Breast
Collagen
Epithelium
Cell Line
Peptides

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

MUC1 alters β-catenin-dependent tumor formation and promotes cellular invasion. / Schroeder, Joyce; Adriance, Melissa C.; Thompson, Melissa C.; Camenisch, Todd D; Gendler, Sandra J.

In: Oncogene, Vol. 22, No. 9, 06.03.2003, p. 1324-1332.

Research output: Contribution to journalArticle

Schroeder, Joyce ; Adriance, Melissa C. ; Thompson, Melissa C. ; Camenisch, Todd D ; Gendler, Sandra J. / MUC1 alters β-catenin-dependent tumor formation and promotes cellular invasion. In: Oncogene. 2003 ; Vol. 22, No. 9. pp. 1324-1332.
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