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.