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Sortilin is associated with breast cancer aggressiveness and contributes to tumor
cell adhesion and invasion
#MMPMID25871389
Roselli S
; Pundavela J
; Demont Y
; Faulkner S
; Keene S
; Attia J
; Jiang CC
; Zhang XD
; Walker MM
; Hondermarck H
Oncotarget
2015[Apr]; 6
(12
): 10473-86
PMID25871389
show ga
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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