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Oncotarget. 2015 Apr 30;6(12):10473-86.

Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion.

Author information

1
School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.
2
Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
3
INSERM U908, IFR-147, Universite Lille 1, Villeneuve d'Ascq 59655, France.
4
INSERM U1138, Equipe 11, Centre de Recherche des Cordeliers, Paris 75006, France.
5
School of Public Health & Medicine, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.

Abstract

The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion.

KEYWORDS:

breast cancer; cell adhesion; cell invasion; protein expression; sortilin

PMID:
25871389
PMCID:
PMC4496368
DOI:
10.18632/oncotarget.3401
[Indexed for MEDLINE]
Free PMC Article

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