title: Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion.
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.
authors: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.|Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
authors: Séverine
authors: S
authors: Roselli
authors: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.|Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
authors: Jay
authors: J
authors: Pundavela
authors: INSERM U908, IFR-147, Universite Lille 1, Villeneuve d'Ascq 59655, France.|INSERM U1138, Equipe 11, Centre de Recherche des Cordeliers, Paris 75006, France.
authors: Yohann
authors: Y
authors: Demont
authors: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.|Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
authors: Sam
authors: S
authors: Faulkner
authors: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.|Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
authors: Sheridan
authors: S
authors: Keene
authors: Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.|School of Public Health & Medicine, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.
authors: John
authors: J
authors: Attia
authors: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.|Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
authors: Chen Chen
authors: CC
authors: Jiang
authors: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.|Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
authors: Xu Dong
authors: XD
authors: Zhang
authors: Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.|School of Public Health & Medicine, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.
authors: Marjorie M
authors: MM
authors: Walker
authors: School of Biomedical Sciences & Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan NSW 2308, Australia.|Hunter Medical Research Institute, University of Newcastle, New Lambton NSW 2305, Australia.
authors: Hubert
authors: H
authors: Hondermarck
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014162:Transfection; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D014408:Biomarkers, Tumor; D000099183:Sortilin
keywords: breast cancer; cell adhesion; cell invasion; protein expression; sortilin