Oncotarget

Research Papers:

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

Séverine Roselli, Jay Pundavela, Yohann Demont, Sam Faulkner, Sheridan Keene, John Attia, Chen Chen Jiang, Xu Dong Zhang, Marjorie M. Walker and Hubert Hondermarck _

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Oncotarget. 2015; 6:10473-10486. https://doi.org/10.18632/oncotarget.3401

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Abstract

Séverine Roselli1,2, Jay Pundavela1,2, Yohann Demont3,5, Sam Faulkner1,2, Sheridan Keene1,2, John Attia2,4, Chen Chen Jiang1,2, Xu Dong Zhang1,2, Marjorie M. Walker2,4, Hubert Hondermarck1,2

1School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia

2Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia

3INSERM U908, IFR-147, Universite Lille 1, Villeneuve d’Ascq 59655, France

4School of Public Health & Medicine, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia

5INSERM U1138, Equipe 11, Centre de Recherche des Cordeliers, Paris 75006, France

Correspondence to:

Hubert Hondermarck, e-mail: [email protected]

Keywords: breast cancer, sortilin, protein expression, cell adhesion, cell invasion

Received: January 21, 2015     Accepted: February 16, 2015     Published: March 18, 2015

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.


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