Anomalous dystroglycan in carcinoma cell lines

Losasso, Carmen; Tommaso, Francesca Di; Sgambato, Alessandro; Ardito, Raffaele; Cittadini, Achille; Giardina, Bruno; Petrucci, Tamara C.; Brancaccio, Andrea

doi:10.1016/s0014-5793(00)02157-8

Cited by 90 publications

(130 citation statements)

References 39 publications

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“…Furthermore, DAG-1 interacts with and regulates caveolin-3 distribution which in turn affects alpha-integrin 7 receptor expression (Sotgia et al, 2000;Cote et al, 2002) so that the hAG/ DAG-1 interaction could be affecting a further receptor pathway. Alpha dystroglycan is almost undetectable in cancer cell lines by Western blotting (Losasso et al, 2000), and this is reflected by the low number of clones (2) obtained from the human breast cancer cell line prey library compared with the placenta library (40). The hAG/DAG-1 interaction could therefore have more of a paracrine function than the hAG/C4.4a interaction, and thus be involved in cell -cell interactions between cancer and noncancer cells and the intervening extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan

et al. 2003

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OX3 9DS, UKhAG-2 and hAG-3 are recently discovered human homologues of the secreted Xenopus laevis proteins XAG-1/2 (AGR-1/2) that are expressed in the cement gland, an ectodermal organ in the head associated with anteroposterior fate determination during early development. Although the roles of hAG-2 and hAG-3 in mammalian cells are unknown, both proteins share a high degree of protein sequence homology and lie adjacent to one another on chromosome 7p21. hAG-2 mRNA expression has previously been demonstrated in oestrogen receptor (ER)-positive cell lines. In this study, we have used real-time quantitative RT -PCR analysis and immunohistochemistry on tissue microarrays to demonstrate concordant expression of hAG-2 and hAG-3 mRNA and protein in breast tumour tissues. Tumour expression of both genes correlated with OR (hAG2, P ¼ 0.0002; hAG-3, P ¼ 0.0012), and inversely correlated with epidermal growth factor receptor (EGFR) (P ¼ 0.003). Yeast two-hybrid cloning identified metastasis-associated GPIanchored C4.4a protein and extracellular alpha-dystroglycan (DAG-1) as binding partners for both hAG-2 and hAG-3, which if replicated in clinical oncology would demonstrate a potential role in tumour metastasis through the regulation of receptor adhesion and functioning. hAG-2 and hAG-3 may therefore serve as useful molecular markers and/or potential therapeutic targets for hormone-responsive breast tumours.

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Section: Discussionmentioning

confidence: 99%

hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan

et al. 2003

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“…6,[28][29][30][31][32] It has been hypothesized that loss of DG expression might play an important role in tumor development by altering the interactions between cells and the surrounding matrix. 7,[10][11][12] From this point of view, DG might act as a tumor suppressor gene and its loss of function could influence the formation of strong contacts between basement membranes and the cytoskeleton of cells, thus favoring tumor development and invasiveness. The exact role of DG in the process of tumor development and in the maintenance of the malignant phenotype, however, remains to be defined.…”

Section: Discussionmentioning

confidence: 99%

“…The transmembrane β-DG anchors α-DG to the cell membrane and is linked to the actin cytoskeleton via dystrophin or its paralogue utrophin. 3,6,9 We and others recently demonstrated that DG expression, and mainly α-DG, is reduced or lost in a variety of human cancer cell lines 7,10,11 and in primary breast, colon and prostate cancers. 11,12 It has been also observed that a reduction in the expression levels of DG is most pronounced in high-grade diseases 11,12 and has a prognostic significance in breast cancer patients.…”

Section: Introductionmentioning

confidence: 95%

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Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Sgambato¹,

Camerini²,

Faraglia³

et al. 2004

Cancer Biology & Therapy

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Dystroglycan (DG) is an adhesion molecule formed by two subunits, α (extracellular) and β (transmembrane) DG, which are codified by a single gene and form a continuous link from the extracellular matrix to the intracellular cytoskeleton. Reduction or loss of expression of DG has been observed in human cancer cell lines and primary tumors and has been suggested to promote tumor development and invasiveness.In this study, the human breast epithelial non-tumorigenic MCF10F and the breast cancer MCF7 cell lines were engineered to stably express an exogenous DG cDNA and the effects on the phenotype of both cell lines were evaluated. The MCF10F transfected cells displayed an increased expression of both DG subunits which was associated with inhibition of the anchorage-dependent growth, accumulation of cells in the G 0 /G 1 phase of the cell cycle and increased adhesion to a substratum. The MCF7 transfected cells were unable to restore α-DG despite an increased expression of the β-DG subunit. Anchoragedependent and independent growth and the in vivo tumorigenicity were reduced in these derivatives that also displayed a reduced adhesion to a substratum and were shown to release α-DG in the culture medium.These findings confirm and extend previous evidence that transformation of mammary epithelial cells is associated with loss of their ability to retain α-DG on the cell membrane. Moreover, they indicate that DG is involved in cell functions other than cell adhesion to the extracellular matrix, and that its loss of function might predispose to tumor progression by compromising regulatory controls over cell growth and proliferation.

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“…In this respect, it must be underlined that DG, and in particular the b-subunit, has been proven to be a sensible target of gelatinases, that are, MMP-2 and MMP-9 (6-9). Thus, a 30-kDa truncated form of b-DG, devoid of a portion of its extracellular N-terminal domain, has been observed in several tumor cell lines, its formation being associated to the enzymatic activity of gelatinases (10,11).…”

Section: Introductionmentioning

confidence: 99%

Enzymatic processing by MMP‐2 and MMP‐9 of wild‐type and mutated mouse β‐dystroglycan

et al. 2012

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SummaryDystroglycan (DG) is a membrane-associated protein complex formed by two noncovalently linked subunits, a-DG, a highly glycosylated extracellular protein, and b-DG, a transmembrane protein. The interface between the two DG subunits, which is crucial to maintain the integrity of the plasma membrane, involves the C-terminal domain of a-DG and the N-terminal extracellular domain of b-DG. It is well known that under both, physiological and pathological conditions, gelatinases (i.e. MMP-9 and/or MMP-2) can degrade DG, disrupting the connection between the extracellular matrix and the cytoskeleton. However, the molecular mechanisms and the exact cleavage sites underlying these events are still largely unknown. In a previous study, we have characterized the enzymatic digestion of the murine b-DG ectodomain by gelatinases, identifying a main cleavage site on the b-DG ectodomain produced by MMP-9. In this article, we have deepened the pattern of the b-DG ectodomain digestion by MMP-2 by using a combined approach based on SDS-PAGE, Orbitrap, and HPLC-ESI-IT mass spectrometry. Furthermore, we have characterized the kinetic parameters of the digestion of some b-DG ectodomain mutants by gelatinases.2012 IUBMB IUBMB Life, 64(12): 988-994, 2012

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Anomalous dystroglycan in carcinoma cell lines

Cited by 90 publications

References 39 publications

hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan

hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan

Increased expression of dystroglycan inhibits the growth and tumorigenicity of human mammary epithelial cells

Enzymatic processing by MMP‐2 and MMP‐9 of wild‐type and mutated mouse β‐dystroglycan

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