Literature DB >> 12538472

Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and real-time PCR analyses.

Amy L Lark1, Chad A Livasy, Benjamin Calvo, Laura Caskey, Dominic T Moore, XiHui Yang, William G Cance.   

Abstract

PURPOSE: Focal adhesion kinase (FAK), a protein tyrosine kinase that functions in signaling events between cells and their extracellular matrix, is overexpressed in a variety of human solid tumors. To determine whether FAK expression is up-regulated in colorectal cancer, we analyzed FAK mRNA and protein levels in primary colorectal tumors and colorectal liver metastases. EXPERIMENTAL
DESIGN: p125(FAK) expression in formalin-fixed paraffin-embedded (FFPE) tissue was studied using immunohistochemical assays on 24 matched primary colorectal carcinomas and colorectal liver metastases as well as 18 different colorectal liver metastases using monoclonal anti-FAK 4.47. FAK mRNA expression was quantitated by real-time PCR on 39 matched normal colorectal mucosa and primary colorectal carcinomas as well as on 17 separate liver metastases.
RESULTS: Elevated levels of p125(FAK) expression were demonstrated in both primary colorectal tumors and colorectal liver metastases compared with normal colorectal mucosa. Immunohistochemistry experiments demonstrated equivalent FAK expression in matched samples of colorectal primary tumors and liver metastases. Using real-time PCR in 39 matched samples, FAK mRNA copy number was significantly higher in primary colorectal tumors compared with normal colorectal mucosa. FAK expression was analyzed by both real-time PCR and immunohistochemistry in a separate set of colorectal liver metastases. Immunohistochemistry demonstrated high levels of FAK expression in 89% of samples. Furthermore, FAK mRNA copies in these unmatched liver metastases were significantly higher than the primary tumor FAK mRNA copies.
CONCLUSION: These experiments have shown that both primary colorectal cancers and colorectal liver metastases express high levels of FAK mRNA and p125(FAK) protein. Furthermore, the majority of colorectal liver metastases demonstrated robust FAK expression equivalent to or greater than that in the primary colorectal tumor.

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Year:  2003        PMID: 12538472

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN: 1078-0432            Impact factor:   12.531


  66 in total

1.  Phosphorylation of focal adhesion kinase at Tyr397 in gastric carcinomas and its clinical significance.

Authors:  I-Rue Lai; Pei-Yu Chu; Hsiao-Sheng Lin; Jun-Yang Liou; Yee-Jee Jan; Jen-Chieh Lee; Tang-Long Shen
Journal:  Am J Pathol       Date:  2010-08-19       Impact factor: 4.307

2.  TGF-beta1 modulates focal adhesion kinase expression in rat intestinal epithelial IEC-6 cells via stimulatory and inhibitory Smad binding elements.

Authors:  Mary F Walsh; Dinakar R Ampasala; Arun K Rishi; Marc D Basson
Journal:  Biochim Biophys Acta       Date:  2008-11-14

3.  Oncogenic Receptor Tyrosine Kinases Directly Phosphorylate Focal Adhesion Kinase (FAK) as a Resistance Mechanism to FAK-Kinase Inhibitors.

Authors:  Timothy A Marlowe; Felicia L Lenzo; Sheila A Figel; Abigail T Grapes; William G Cance
Journal:  Mol Cancer Ther       Date:  2016-09-16       Impact factor: 6.261

4.  RhoC promotes metastasis via activation of the Pyk2 pathway in prostate cancer.

Authors:  Megumi Iiizumi; Sucharita Bandyopadhyay; Sudha K Pai; Misako Watabe; Shigeru Hirota; Sadahiro Hosobe; Taisei Tsukada; Kunio Miura; Ken Saito; Eiji Furuta; Wen Liu; Fei Xing; Hiroshi Okuda; Aya Kobayashi; Kounosuke Watabe
Journal:  Cancer Res       Date:  2008-09-15       Impact factor: 12.701

5.  From tumorigenesis to microenvironment and immunoregulation: the many faces of focal adhesion kinase and challenges associated with targeting this elusive protein.

Authors:  Felicia L Lenzo; William G Cance
Journal:  Transl Cancer Res       Date:  2017-08       Impact factor: 1.241

6.  The prognostic significance of focal adhesion kinase expression in stage I non-small-cell lung cancer.

Authors:  Grace K Dy; Lourdes Ylagan; Saraswati Pokharel; Austin Miller; Elizabeth Brese; Wiam Bshara; Carl Morrison; William G Cance; Vita M Golubovskaya
Journal:  J Thorac Oncol       Date:  2014-09       Impact factor: 15.609

7.  p53 regulates FAK expression in human tumor cells.

Authors:  Vita M Golubovskaya; Richard Finch; Frederick Kweh; Nicole A Massoll; Martha Campbell-Thompson; Margaret R Wallace; William G Cance
Journal:  Mol Carcinog       Date:  2008-05       Impact factor: 4.784

8.  Biological resonance for cancer metastasis, a new hypothesis based on comparisons between primary cancers and metastases.

Authors:  Dongwei Gao; Sha Li
Journal:  Cancer Microenviron       Date:  2013-11-10

Review 9.  Targeting Pyk2 for therapeutic intervention.

Authors:  Christopher A Lipinski; Joseph C Loftus
Journal:  Expert Opin Ther Targets       Date:  2010-01       Impact factor: 6.902

Review 10.  Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics.

Authors:  William G Cance; Elena Kurenova; Timothy Marlowe; Vita Golubovskaya
Journal:  Sci Signal       Date:  2013-03-26       Impact factor: 8.192

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