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Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer

Author:
  • Astrid Escudero-Esparza
  • Michael Bartoschek
  • Chrysostomi Gialeli
  • Marcin Okroj
  • Sioned Owen
  • Karin Jirström
  • Akira Orimo
  • Wen G. Jiang
  • Kristian Pietras
  • Anna M. Blom
Publishing year: 2016
Language: English
Pages: 76920-76933
Publication/Series: Oncotarget
Volume: 7
Issue: 47
Document type: Journal article
Publisher: Impact Journals, LLC

Abstract english

Human CUB and Sushi multiple domains 1 (CSMD1) is a membrane-bound complement inhibitor suggested to act as a putative tumor suppressor gene, since allelic loss of this region encompassing 8p23 including CSMD1 characterizes various malignancies. Here, we assessed the role of CSMD1 as a tumor suppressor gene in the development of breast cancer in vitro and in vivo. We found that human breast tumor tissues expressed CSMD1 at lower levels compared to that in normal mammary tissues. The decreased expression of CSMD1 was linked to a shorter overall survival of breast cancer patients. We also revealed that expression of CSMD1 in human breast cancer cells BT-20 and MDA-MB-231 significantly inhibited their malignant phenotypes, including migration, adhesion and invasion. Conversely, stable silencing of CSMD1 expression in T47D cells enhanced cancer cell migratory, adherent and clonogenic abilities. Moreover, expression of CSMD1 in the highly invasive MDA-MB-231 cells diminished their signaling potential as well as their stem cell-like properties as assessed by measurement of aldehyde dehydrogenase activity. In a xenograft model, expression of CSMD1 blocked the ability of cancer cells to metastasize to secondary sites in vivo, likely via inhibiting local invasion but not the extravasation into distant tissues. Taken together, these findings demonstrate the role of CSMD1 as a tumor suppressor gene in breast cancer.

Keywords

  • Cancer and Oncology
  • Medical Genetics
  • Breast cancer
  • Complement system
  • CSMD1
  • Invasion
  • Tumor suppressor

Other

Published
  • Protein Chemistry, Malmö
  • Experimental oncology
  • Personalized Pathology & Cancer Therapy
  • ISSN: 1949-2553
Kristian Pietras
E-mail: kristian [dot] pietras [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 29

MV404 A31B1

90

Project manager

Experimental oncology