Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion

Mohamed Kamal, Deborah L Holliday, Ewan E Morrison, Valerie Speirs, Carmel Toomes, Sandra M Bell

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line. Suppression of CSMD1 significantly increased the proliferation, cell migration and invasiveness of MCF10A cells compared to shcontrols. shCSMD1 cells also showed significantly reduced adhesion to Matrigel and fibronectin. In a three-dimensional Matrigel model of MCF10A cells, reduced CSMD1 expression resulted in the development of larger and more poorly differentiated breast acini-like structures that displayed impaired lumen formation. Loss of CSMD1 expression disrupts a model of mammary duct formation while enhancing proliferation, migration and invasion. Our data suggest that CSMD1 is involved in the suppression of a transformed phenotype.

Original languageEnglish
Pages (from-to)283-292
Number of pages10
JournalOncology Reports
Volume38
Issue number1
Early online date22 May 2017
DOIs
Publication statusPublished - Jul 2017

Fingerprint

Breast
Cell Line
Neoplasms
Fibronectins
Small Interfering RNA
Cell Movement
Chromosomes
Breast Neoplasms
Phenotype
Genes
matrigel

Keywords

  • Apoptosis
  • Breast Neoplasms
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Humans
  • Mammary Glands, Human
  • Membrane Proteins
  • Neoplasm Invasiveness
  • RNA, Small Interfering
  • Journal Article

Cite this

Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion. / Kamal, Mohamed; Holliday, Deborah L; Morrison, Ewan E; Speirs, Valerie; Toomes, Carmel; Bell, Sandra M.

In: Oncology Reports, Vol. 38, No. 1, 07.2017, p. 283-292.

Research output: Contribution to journalArticle

Kamal, Mohamed ; Holliday, Deborah L ; Morrison, Ewan E ; Speirs, Valerie ; Toomes, Carmel ; Bell, Sandra M. / Loss of CSMD1 expression disrupts mammary duct formation while enhancing proliferation, migration and invasion. In: Oncology Reports. 2017 ; Vol. 38, No. 1. pp. 283-292.
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abstract = "The CUB and sushi multiple domains 1 (CSMD1) gene maps to chromosome 8p23, a region deleted in many cancers. Loss of CSMD1 expression is associated with poor prognosis in breast cancer suggesting that it acts as a tumour suppressor in this cancer. However, the function of CSMD1 is largely unknown. Herein, we investigated CSMD1 functions in cell line models. CSMD1 expression was suppressed in MCF10A and LNCaP cells using short hairpin RNA. Functional assays were performed focusing on the 'normal' MCF10A cell line. Suppression of CSMD1 significantly increased the proliferation, cell migration and invasiveness of MCF10A cells compared to shcontrols. shCSMD1 cells also showed significantly reduced adhesion to Matrigel and fibronectin. In a three-dimensional Matrigel model of MCF10A cells, reduced CSMD1 expression resulted in the development of larger and more poorly differentiated breast acini-like structures that displayed impaired lumen formation. Loss of CSMD1 expression disrupts a model of mammary duct formation while enhancing proliferation, migration and invasion. Our data suggest that CSMD1 is involved in the suppression of a transformed phenotype.",
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