Inhibition of Ku heterodimer DNA end binding activity during granulocytic differentiation of human promyelocytic cell lines

Müller, Cathérine; Monferran, Sylvie; Gamp, Alexander-Christopher; Calsou, Patrick; Salles, Bernard

doi:10.1038/sj.onc.1204571

Cited by 22 publications

(26 citation statements)

References 65 publications

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“…The electrophoretic mobility of the protein -DNA complexes was analyzed in 5% (w/v) polyacrylamide gel as described. 33 Note that the non-specific band observed is specific for hamster cell extracts. B, Western blot: 100 mg of whole-cell extracts of CHO-K1 cells, xrs-6 cells and xrs-6 transfectants containing either hamster or human Ku80 cDNA (clone 1 and clone 2) were run on a 10% polyacrylamide gels under reducing conditions.…”

Section: Cell Surface-associated Ku Supports Adhesion Of Cho Cells Onmentioning

confidence: 95%

The Membrane-associated Form of the DNA Repair Protein Ku is Involved in Cell Adhesion to Fibronectin

Monferran

Müller

Mourey

et al. 2004

Journal of Molecular Biology

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The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double-strand breaks recognition and repair. However, Ku is expressed also on the surface of different types of cells along with its intracellular pool within the nucleus and the cytoplasm. Participation of membrane-associated Ku in cell-cell interaction has been reported recently. Here, we describe a novel function of cell-surface Ku as an adhesion receptor for fibronectin (Fn). The role of Ku in cell adhesion was investigated by comparing the Ku80 deficient Chinese hamster ovary (CHO) cell line, xrs-6, with clones transfected stably with either the hamster or human Ku80 cDNA. Ku expression in transfectant cells resulted in a significant increased adhesion on Fn and type IV collagen as compared to control cells. The observed increase in cell adhesion relied on Ku cell-surface expression, since antibodies directed against Ku70 or Ku80 subunit inhibited adhesion on Fn of Ku80, but not control vector, transfected xrs-6 cells. In addition, both Ku70 and Ku80 present a structural relationship with integrin I (or A) domains and the A1 and A3 domains of von Willebrand factor, domains known to be involved in Fn binding. Both Ku70 and Ku80 exhibit a complete set of residues compatible in their position and chemical nature with the formation of a metal ion-dependent adhesion (MIDAS) site implicated in ligand binding and integrin activation. Taken together, these functional and structural approaches support a new role for Ku as an adhesion receptor for Fn.

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Section: Cell Surface-associated Ku Supports Adhesion Of Cho Cells Onmentioning

confidence: 95%

The Membrane-associated Form of the DNA Repair Protein Ku is Involved in Cell Adhesion to Fibronectin

Monferran

Müller

Mourey

et al. 2004

Journal of Molecular Biology

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“…Total proteins were extracted as described previously (52). Proteins (50 μg) were electrophoresed on SDS-PAGE and transferred onto PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells

et al. 2017

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“…Whole cell extracts and immunoblots were prepared as previously described (25). All the antibodies used in our study are presented in Supplementary Information.…”

Section: Western Blot Analysismentioning

confidence: 99%

Cancer-Associated Adipocytes Exhibit an Activated Phenotype and Contribute to Breast Cancer Invasion

et al. 2011

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Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and mature adipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and human tumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, using an original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit an altered phenotype in terms of delipidation and decreased adipocyte markers associated with the occurrence of an activated state characterized by overexpression of proteases, including matrix metalloproteinase-11, and proinflammatory cytokines [interleukin (IL)-6, IL-1b]. In the case of IL-6, we show that it plays a key role in the acquired proinvasive effect by tumor cells. Equally important, we confirm the presence of these modified adipocytes in human breast tumors by immunohistochemistry and quantitative PCR. Interestingly, the tumors of larger size and/or with lymph nodes involvement exhibit the higher levels of IL-6 in tumor surrounding adipocytes. Collectively, all our data provide in vitro and in vivo evidence that (i) invasive cancer cells dramatically impact surrounding adipocytes; (ii) peritumoral adipocytes exhibit a modified phenotype and specific biological features sufficient to be named cancer-associated adipocytes (CAA); and (iii) CAAs modify the cancer cell characteristics/phenotype leading to a more aggressive behavior. Our results strongly support the innovative concept that adipocytes participate in a highly complex vicious cycle orchestrated by cancer cells to promote tumor progression that might be amplified in obese patients. Cancer Res; 71(7); 2455-65. Ó2011 AACR.

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Inhibition of Ku heterodimer DNA end binding activity during granulocytic differentiation of human promyelocytic cell lines

Cited by 22 publications

References 65 publications

The Membrane-associated Form of the DNA Repair Protein Ku is Involved in Cell Adhesion to Fibronectin

The Membrane-associated Form of the DNA Repair Protein Ku is Involved in Cell Adhesion to Fibronectin

Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells

Cancer-Associated Adipocytes Exhibit an Activated Phenotype and Contribute to Breast Cancer Invasion

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