High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype

Abstract

Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive breast cancer that regulates antiapoptotic signaling. We have examined FAK expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples from a large population-based, case-control study of women participating in the University of North Carolina Breast Specialized Programs of Research Excellence (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed, paraffin-embedded tissue sections were stained for FAK and scored as high (3 þ or 4 þ intensity and Z90% positive cells) or otherwise. High FAK expression was associated with poor prognostic indicators including high mitotic index (410 mitoses per 10 consecutive highpower fields), nuclear grade 3, architectural grade 3, estrogen and progesterone receptor negative, and HER-2/ neu overexpressed using CB11 antibody. The association of high FAK expression with HER-2/neu overexpression lends further support that HER-2/neu and FAK collaborate to promote tumorigenesis. The presence of strong FAK expression in many high grade, estrogen-and progesterone-negative breast carcinomas indicates that FAK may be an attractive target for therapeutic intervention.

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

“…By contrast, deletion of FAK in endothelial cells resulted in an increase in apoptosis in vivo, leading to lethality before day 10.5 due to extensive haemorrhaging (Braren et al, 2006). Interestingly, whereas fibroblasts isolated from FAK -/-embryos had defects in migration but not survival, FAK -/-endothelial cells in vivo did not show defects in migration but did undergo apoptosis (Judson et al, 1999;Lark et al, 2003;Lark et al, 2005;Lightfoot et al, 2004;Owens et al, 1995;Owens et al, 1996). Together, these data indicate that how FAK controls cell survival depends very much on cellular origin as well as environmental context.…”

The Lysyl Oxidase Pro-peptide Attenuates Fibronectin-mediated Activation of Focal Adhesion Kinase and p130Cas in Breast Cancer Cells

“…Moreover, their expression is associated with advanced and aggressive phenotype (33,34). Thus, the findings of the inhibitory effect of LOX-PP on this pivotal signaling node suggest that further investigation of its therapeutic potential to inhibit invasive cancers should be investigated.…”

Activation of KLF8 Transcription by Focal Adhesion Kinase in Human Ovarian Epithelial and Cancer Cells

“…Understanding the molecular mechanisms underlying ovarian cancer progression is urgent for developing new strategies for early diagnosis and therapies required for improvement of patient survival. As found in many other types of human tumors (2,3), overexpression or hyperactivation of focal adhesion kinase (FAK) 2 has recently been found in most ovarian cancers, where it is highly associated with high aggressiveness and poor patient survival (4 -7). However, the molecular mechanisms by which FAK contributes to the initiation and progression of ovarian cancer are still poorly understood.…”