Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas

Oktay, Maja H.; Oktay, Kutluk; Hamele‐Bena, Diane; Büyük, Arzu; Koss, Leopold G.

doi:10.1053/hupa.2003.40

Cited by 105 publications

(86 citation statements)

References 21 publications

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“…Elevated FAK levels were reported previously to occur in a subset of early-stage cancers such as DCIS of breast 32,33 and advanced breast cancer and metastatic nodules. 34 -37 However, other studies failed to observe Tumorigenesis and Cancer Progression 1547 AJP November 2008, Vol.…”

Section: Discussionmentioning

confidence: 99%

Focal Adhesion Kinase-Related Proline-Rich Tyrosine Kinase 2 and Focal Adhesion Kinase Are Co-Overexpressed in Early-Stage and Invasive ErbB-2-Positive Breast Cancer and Cooperate for Breast Cancer Cell Tumorigenesis and Invasiveness

Behmoaram

Bijian

Shi

et al. 2008

The American Journal of Pathology

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Malignant tumor cells invade surrounding normal tissue and disseminate to distant organs through a multistep and multifactorial process. In general, the acquisition of early autonomous motile property involves cell polarization toward blood and lymphatic vessels in response to chemotactic signals, cell cytoskeleton remodeling, and formation of cell plasma membrane protrusions. The latter are the site of dynamic turnover of multiple focal adhesion molecules, which allow formation of stable cellmatrix attachments near the leading edge of the protrusions, forward movement of the cell body, and disassembly of focal-matrix adhesions and retraction at the trailing edge. These processes are the driving force for early cancer cell migration and invasion.Central to the regulation of the cell migration cycle is the focal adhesion kinase (FAK) and its homologous FAKrelated proline-rich tyrosine kinase 2 (Pyk2).1 FAK and Pyk2 share 45% amino acid sequence homology with a

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Section: Discussionmentioning

confidence: 99%

Focal Adhesion Kinase-Related Proline-Rich Tyrosine Kinase 2 and Focal Adhesion Kinase Are Co-Overexpressed in Early-Stage and Invasive ErbB-2-Positive Breast Cancer and Cooperate for Breast Cancer Cell Tumorigenesis and Invasiveness

Behmoaram

Bijian

Shi

et al. 2008

The American Journal of Pathology

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“…Analyses of breast cancer tumor samples have revealed that elevated FAK expression is correlated with the development of benign ductal hyperplasia into invasive carcinomas (Oktay et al, 2003;Lightfoot et al, 2004). Here, we have inhibited FAK activity or FAK expression in murine 4T1 breast carcinoma cells via transient FRNK or stable anti-FAK short hairpin RNA (shRNA) expression, respectively.…”

Section: Introductionmentioning

confidence: 99%

Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model

Lim

et al. 2006

Oncogene

105

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Expression of focal adhesion kinase (FAK) is elevated in malignant breast cancer, yet the role of intrinsic FAK activity in promoting tumor progression remains undefined. Here, we have inhibited FAK activity or expression in murine 4T1 breast carcinoma cells via dominantnegative focal adhesion kinase-related non-kinase (FRNK) or anti-FAK short hairpin RNA (shRNA) expression, respectively. Neither FRNK nor FAK shRNA (B80% reduced FAK levels) affected 4T1 proliferation in culture, whereas reduced FAK activity or expression blocked 4T1 cell invasion through Matrigel and resulted in 2-3-fold lower urokinase plasminogen activator (uPA) expression. Control 4T1 cells implanted into mammary fat pads of BALB/c mice exhibited spontaneous metastasis to the lungs, to the peritoneal cavity, and resulted in 90% lethality within 21 days. Whereas FAK shRNAexpressing 4T1 cells formed tumors in mice with low levels of apoptosis, when mammary-injected, these cells did not exhibit lung metastasis after 21 days and caused only 40% lethality up to 60 days. Transient re-expression of wildtype but not kinase-dead FAK in 4T1 FAK shRNA cells promoted uPA production and mammary to lung metastasis within 7 days. In fact, stable human uPA overexpression in 4T1 FAK shRNA cells promoted Matrigel invasion and lung metastasis equal to 4T1 controls. Conversely, treatment with plasminogen activator inhibitor-1 or neutralizing antibody to uPA blocked Matrigel invasion of 4T1 control cells. These studies provide the first direct proof that FAK catalytic activity can facilitate metastatic breast cancer progression by regulating uPA expression.

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“…In our lab, human FAK was subsequently identified in high-grade sarcomas 12 and breast tumors. [13][14][15] FAK is overexpressed in a variety of human tumors in comparison with adjacent normal tissue, including breast, [13][14][15][16] colon, 13,14,17,18 thyroid, 19 ovarian, 20 cervix, 16 head and neck, 21 and esophagus. 22 Early work suggested that FAK might function in the later stages of tumor progression, such as invasion and metastasis, promoting adhesion in invading cells.…”

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confidence: 99%

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

et al. 2005

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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.

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Focal adhesion kinase as a marker of malignant phenotype in breast and cervical carcinomas

Cited by 105 publications

References 21 publications

Focal Adhesion Kinase-Related Proline-Rich Tyrosine Kinase 2 and Focal Adhesion Kinase Are Co-Overexpressed in Early-Stage and Invasive ErbB-2-Positive Breast Cancer and Cooperate for Breast Cancer Cell Tumorigenesis and Invasiveness

Focal Adhesion Kinase-Related Proline-Rich Tyrosine Kinase 2 and Focal Adhesion Kinase Are Co-Overexpressed in Early-Stage and Invasive ErbB-2-Positive Breast Cancer and Cooperate for Breast Cancer Cell Tumorigenesis and Invasiveness

Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model

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

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