The C‐terminal domain of focal adhesion kinase reduces the tumor cell invasiveness in chondrosarcoma cell lines
- 1 November 2003
- journal article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 21 (6), 1071-1080
- https://doi.org/10.1016/s0736-0266(03)00101-3
Abstract
Human chondrosarcoma is a malignancy that has no effective systemic therapy, making the interruption of the metastatic cascade critical to enhance patient survival. The processes of local invasion and metastases share similar mechanisms at a cellular level. Focal adhesion kinase (FAK) has been implicated in local invasion of malignant tumor cells. In the current manuscript we examine the effect of FAK inhibition on cell attachment to extracellular matrix (ECM) and in vitro invasion. Bovine articular chondrocytes and two human chondrosarcoma cell lines were utilized to examine FAK activity in tumor cell invasiveness. Endogenous FAK activity was inhibited by adenoviral transfection with the C-terminal domain of FAK. This inhibition resulted from decreased FAK phosphorylation, while FAK expression remained unchanged. Inhibition of FAK phosphorylation and hence its activity lead to decreased cell adhesion to Type II collagen and decreased cell invasiveness. These effects were not due to changes in integrin expression, indicating that the inhibition was the result of disruption of outside: in signaling. There are three important aspects to these results. The first is that interruption of transmembrane signaling can affect cell attachment. The second is that in chondrosarcoma, cell differentiation correlates with FAK expression and metastatic potential. Thirdly, that cell invasiveness correlates with FAK activity and implies a mechanistic role for this molecular complex in local invasion and metastasis.Keywords
This publication has 40 references indexed in Scilit:
- The involvement of β1 integrin in the modulation by collagen of chondrocyte‐response to transforming growth factor‐β1Journal of Orthopaedic Research, 2002
- CAS/Crk Coupling Serves as a “Molecular Switch” for Induction of Cell MigrationThe Journal of cell biology, 1998
- Signaling through focal adhesion kinaseBioEssays, 1997
- Metastasis of chondrosarcomaZeitschrift für Krebsforschung und Klinische Onkologie, 1996
- Integrins: Emerging Paradigms of Signal TransductionAnnual Review of Cell and Developmental Biology, 1995
- Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient miceNature, 1995
- Immunohistochemical localization of collagenous proteins in cartilaginous tumors: characteristic distribution of type IX collagenZeitschrift für Krebsforschung und Klinische Onkologie, 1993
- Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly.The Journal of cell biology, 1992
- The Effects of Long Term Monolayer Culture on the Proteoglycan Phenotype of a Clonal Population of Mature Human Malignant ChondrocytesConnective Tissue Research, 1991
- A Comparison of Collagen Synthesis by Different Categories of Human Chondrosarcoma in Organ CulturePublished by Ovid Technologies (Wolters Kluwer Health) ,1982