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Pro-Apoptotic and Anti-Invasive Properties Underscore the Tumor-Suppressing Impact of Myoglobin on a Subset of Human Breast Cancer Cells.
Aboouf, Mostafa A; Armbruster, Julia; Thiersch, Markus; Guscetti, Franco; Kristiansen, Glen; Schraml, Peter; Bicker, Anne; Petry, Ruben; Hankeln, Thomas; Gassmann, Max; Gorr, Thomas A.
Afiliación
  • Aboouf MA; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
  • Armbruster J; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
  • Thiersch M; Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
  • Guscetti F; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
  • Kristiansen G; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
  • Schraml P; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
  • Bicker A; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
  • Petry R; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
  • Hankeln T; Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
  • Gassmann M; Institute of Pathology, University Hospital Bonn, University of Bonn, D-53127 Bonn, Germany.
  • Gorr TA; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
Int J Mol Sci ; 23(19)2022 Sep 29.
Article en En | MEDLINE | ID: mdl-36232784
ABSTRACT
The expression of myoglobin (MB), well known as the oxygen storage and transport protein of myocytes, is a novel hallmark of the luminal subtype in breast cancer patients and correlates with better prognosis. The mechanisms by which MB impacts mammary tumorigenesis are hitherto unclear. We aimed to unravel this role by using CRISPR/Cas9 technology to generate MB-deficient clones of MCF7 and SKBR3 breast cancer cell lines and subsequently characterize them by transcriptomics plus molecular and functional analyses. As main findings, loss of MB at normoxia upregulated the expression of cell cyclins and increased cell survival, while it prevented apoptosis in MCF7 cells. Additionally, MB-deficient cells were less sensitive to doxorubicin but not ionizing radiation. Under hypoxia, the loss of MB enhanced the partial epithelial to mesenchymal transition, thus, augmenting the migratory and invasive behavior of cells. Notably, in human invasive mammary ductal carcinoma tissues, MB and apoptotic marker levels were positively correlated. In addition, MB protein expression in invasive ductal carcinomas was associated with a positive prognostic value, independent of the known tumor suppressor p53. In conclusion, we provide multiple lines of evidence that endogenous MB in cancer cells by itself exerts novel tumor-suppressive roles through which it can reduce cancer malignancy.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Mioglobina Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Mioglobina Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Suiza