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Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer

Escudero-Esparza, Astrid LU ; Bartoschek, Michael LU ; Gialeli, Chrysostomi LU ; Okroj, Marcin LU ; Owen, Sioned; Jirström, Karin LU ; Orimo, Akira; Jiang, Wen G.; Pietras, Kristian LU and Blom, Anna M. LU (2016) In Oncotarget 7(47). p.76920-76933
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Complement system, CSMD1, Invasion, Tumor suppressor
in
Oncotarget
volume
7
issue
47
pages
14 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:84999053484
  • wos:000389633400048
ISSN
1949-2553
DOI
10.18632/oncotarget.12729
language
English
LU publication?
yes
id
4c845440-2e88-4841-b13d-103e36c1e766
date added to LUP
2016-12-30 12:36:49
date last changed
2017-11-05 05:11:50
@article{4c845440-2e88-4841-b13d-103e36c1e766,
  abstract     = {<p>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.</p>},
  author       = {Escudero-Esparza, Astrid and Bartoschek, Michael and Gialeli, Chrysostomi and Okroj, Marcin and Owen, Sioned and Jirström, Karin and Orimo, Akira and Jiang, Wen G. and Pietras, Kristian and Blom, Anna M.},
  issn         = {1949-2553},
  keyword      = {Breast cancer,Complement system,CSMD1,Invasion,Tumor suppressor},
  language     = {eng},
  number       = {47},
  pages        = {76920--76933},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer},
  url          = {http://dx.doi.org/10.18632/oncotarget.12729},
  volume       = {7},
  year         = {2016},
}