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.

p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma

“…Similar results were reported in melanoma, expressing Trks, p75 NTR and sortilin, wherein cell migration and invasion induced by pro-NGF were depending on p75 NTR [50]. However, sortilin “ per se ” has been recently described to inhibit cell adhesion in colorectal cancer cell lines [51] and to activate breast cancer cell migration and invasiveness [52]. These mechanisms depend on focal adhesion kinase (FAK) and Src activations, [52, 53] without any change in apoptotic or proliferative cancer cell functions [52].…”

“…However, sortilin “ per se ” has been recently described to inhibit cell adhesion in colorectal cancer cell lines [51] and to activate breast cancer cell migration and invasiveness [52]. These mechanisms depend on focal adhesion kinase (FAK) and Src activations, [52, 53] without any change in apoptotic or proliferative cancer cell functions [52]. However, in RCC cells, our results suggest that the role of sortilin is not crucial for p75 NTR function through pro-BDNF activation as assessed by the decrease but not suppression of AKT / ERK activation.…”

Insights into the role of sulfated glycans in cancer cell adhesion and migration through use of branched peptide probe

“…LRP receptors and sortilin are both known to play a role in cell adhesion, migration and differentiation3132333435, though as in the case of HSPG, the molecular mechanism underlying their complex functions is far from clear.…”

The signal peptide as a new target for drug design

“…[89][90][91] Interest on the downmodulation of sortilin in breast cancer treatment is increasing as it is associated with breast cancer metastatic potential. 92 Furthermore, sortilin is highly expressed in breast cancer cell lines compared to nontumorigenic epithelial cells. Because sortilin binds to progranulin, its regulation could be beneficial to halting breast cancer progression.…”