Focal adhesion kinase interacts with the transcriptional coactivator FHL2 and both are overexpressed in epithelial ovarian cancer.
Abnormal signal transduction arising from integrins and protein tyrosine kinases has been implicated in the initiation and progression of a variety of human cancers. Integrin-mediated signal transduction pathways require regulated cytoplasmic protein-protein interactions. However, little is known about integrin-associated proteins and ovarian cancer. In our study we investigated the association of pp125FAK, a cytoplasmic tyrosine kinase, involved in anchorage-independent growth of tumor cells, and the Four and a Half LIM domain (FHL) protein FHL2, which was recently shown to interact with integrins. Our data demonstrated that pp125FAK and FHL2 form a protein complex in human ovarian carcinoma. Furthermore, we showed that pp125FAK is overexpressed in epithelial ovarian cancer, but virtually absent in normal ovary. Our immunohistochemistry data showed that FHL2 protein expression is also augmented in epithelial ovarian cancer. Taken together, our results demonstrated for the first time FHL2 expression in human ovarian cancer cells, suggesting an important functional role of pp125FAK and FHL2 complex in gynecologic malignancies.
Gabriel
Boris
B
Universitäts-Frauenklinik, Klinikum der Universität Freiburg, Freiburg, Germany. bGabriel@frk.ukl.uni-freiburg.de
Mildenberger
Stephan
S
Weisser
Christian W
CW
Metzger
Eric
E
Gitsch
Gerald
G
Schüle
Roland
R
Müller
Judith M
JM
D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*
C105987:FHL2 protein, human; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009124:Muscle Proteins; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human