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 language | English |
|---|---|
| Pages (from-to) | 283-292 |
| Number of pages | 10 |
| Journal | Oncology Reports |
| Volume | 38 |
| Issue number | 1 |
| Early online date | 22 May 2017 |
| DOIs | |
| Publication status | Published - Jul 2017 |
| Externally published | Yes |
Bibliographical note
This study was supported by an Egyptian Government scholarship to M.K. and grants from Yorkshire Cancer Research grant number L292 (S.M.B.) and Breast Cancer Research Campaign grant numbers 2007NovPR53 (S.M.B. and V.S.) and 2008NovPR04 (D.H. and V.S.).Keywords
- Apoptosis
- Breast Neoplasms
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- Female
- Humans
- Mammary Glands, Human
- Membrane Proteins
- Neoplasm Invasiveness
- RNA, Small Interfering
- Journal Article
