Original ContributionsFocal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas☆
Section snippets
Immunohistochemistry
The cases were retrieved from the files of the Montefiore Medical Center Department of Pathology. Sixty cases were evaluated for FAK expression, including 17 cases of cervical dysplasia (CIN I and CIN I-II), 14 cases of carcinoma in situ (CIS) of the cervix, and 16 cases of invasive SCC of the cervix. In addition, 13 cases of atypical ductal hyperplasia of the breast, 8 cases of invasive carcinoma and 7 cases of ductal carcinoma in situ (DCIS) of the breast, and 4 cases of benign breast tissue
FAK expression in cervical carcinoma
Routine histological analysis and grading of all lesions was performed before immunohistochemical analysis of FAK expression. Of the 16 cases of invasive SCC of the cervix, 50% were graded as poorly differentiated tumors and the 50% as moderately differentiated tumors. Two cases of moderately differentiated SCC and 2 cases of poorly differentiated SCC contained normal squamous epithelium on the same slide that served as internal controls. Thirteen of 16 cases of invasive SCC stained strongly
Discussion
A large body of evidence supports the role of FAK in regulation of cell proliferation, survival, and migration. Detailed molecular analyses have demonstrated that the versatility of FAK functions is due to its unique structure that enables it to act as a “scaffold” for the assembly of the multiprotein signaling complexes.7, 8 Thus FAK acts as a linker of transmembrane receptors with the major growth regulatory pathways, including extracellular signal-related kinase and c-Jun-N-terminal
References (24)
- et al.
Signaling through focal adhesion kinase
Prog Biophys Mol Biol
(1999) - et al.
Overexpression of the focal adhesion kinase (p125FAK) in the vascular smooth muscle cells of intimal hyperplasia
J Vasc Surg
(2001) - et al.
Typing of human papilloma viruses by polymerase chain reaction amplification with L1 primers and RFLP analysis
Mol Cell Probes
(1992) - et al.
Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol 3-kinase
J Biol Chem
(1996) - et al.
Control of cell cycle progression by fibronectin matrix architecture
J Biol Chem
(1998) - et al.
Expression of focal adhesion kinase gene in invasive cancer
Lancet
(1993) - et al.
Integrin signaling
Science
(1999) Focal adhesion kinase and its potential involvement in tumor invasion and metastasis
Head Neck
(1998)- et al.
Activation of the focal adhesion kinase signal transduction pathway in cervical carcinoma cell lines and human genital epithelial cells immortalized with human papillomavirus type 18
Oncogene
(1997) - et al.
Monoclonal antibodies to individual tyrosine phosphorylated protein substrates of oncogene-encoded tyrosine kinases
Proc Natl Acad Sci U S A
(1990)
pp125 FAK, a structurally distinctive protein tyrosine kinase associated with focal adhesions
Proc Natl Acad Sci U S A
Integrin-mediated signal transduction linked ras pathway by GRB2 binding to focal adhesion kinase
Nature
Cited by (111)
In vivo modeling of the EGFR family in breast cancer progression and therapeutic approaches
2020, Advances in Cancer ResearchCircular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and influence FAK phosphorylation
2019, EBioMedicineCitation Excerpt :We found that knocking down STEAP4 led to a more invasive phenotype of BC cells, while overexpression STEAP4 exerted an opposite function. FAK is a well-studied tyrosine kinase that is abnormally elevated in many cancers, such as lung, ovarian, breast, cervical, and bladder cancer [46–50]. FAK can influence fundamental oncogenic cellular behaviours, including adhesion, migration, proliferation and angiogenesis, and it is closely related to metastasis and poor survival [51].
HPW-RX40 restores anoikis sensitivity of human breast cancer cells by inhibiting integrin/FAK signaling
2015, Toxicology and Applied PharmacologyCitation Excerpt :β1 integrin has been suggested to be the major mediators of cancer cell–cell adhesion or aggregation (Casey et al., 2001; Ivascu and Kubbies, 2007; Robinson et al., 2003). Furthermore, overexpressed β1 integrin is critical for induction, invasion, and metastatic potential of a wide variety of human cancers, including breast cancer (Arboleda et al., 2003; Graff et al., 2001; Oktay et al., 2003; White et al., 2004). Upon activation by ligand binding, integrins activate downstream effectors and generate a signaling platform containing a large number of adaptor proteins and kinases.
- ☆
0046-8177/03/3403-0007$30.00/0