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CD74-dependent Deregulation of the Tumor Suppressor Scribble in Human Epithelial and Breast Cancer Cells

Metodieva, Gergana and Nogueira-de-Souza, Naiara Correa and Greenwood, Christina and Al-Janabi, Khalid and Leng, Lin and Bucala, Richard and Metodiev, Metodi V (2013) 'CD74-dependent Deregulation of the Tumor Suppressor Scribble in Human Epithelial and Breast Cancer Cells.' Neoplasia, 15 (6). 660-IN21. ISSN 1476-5586


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The γ subunit of the major histocompatibility complex (MHC) class II complex, CD74, is overexpressed in a significant proportion of metastatic breast tumors, but the mechanistic foundation and biologic significance of this phenomenon are not fully understood. Here, we show that when CD74 is overexpressed in human cancer and noncancerous epithelial cells, it interacts and interferes with the function of Scribble, a product of a well-known tumor suppressor gene. Furthermore, using epithelial cell lines expressing CD74 under the control of tetracycline-inducible promoter and quantitative high-resolution mass spectrometry, we demonstrate that, as a result of CD74 overexpression, the phosphorylation pattern of the C-terminal part of Scribble undergoes specific changes. This is accompanied with a translocation of the protein from the sites of cell-to-cell contacts at the plasma membrane to the cytoplasm, which is likely to effectively enhance the motility and invasiveness of the cancer cells. © 2013 Neoplasia Press, Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Cell Line; Cell Line, Tumor; Cell Membrane; Cytoplasm; Epithelial Cells; Humans; Breast Neoplasms; Membrane Proteins; Tumor Suppressor Proteins; Antigens, Differentiation, B-Lymphocyte; Histocompatibility Antigens Class II; Gene Expression Regulation; Amino Acid Sequence; Phosphorylation; Molecular Sequence Data; Female; Promoter Regions, Genetic; Gene Knockdown Techniques
Subjects: R Medicine > RB Pathology
R Medicine > RZ Other systems of medicine
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 10 Jun 2013 15:35
Last Modified: 23 Sep 2022 18:47

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