Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-β signaling and metastasis
Open Access
- 9 September 2009
- journal article
- Published by Springer Science and Business Media LLC in Breast Cancer Research
- Vol. 11 (5), R68
- https://doi.org/10.1186/bcr2360
Abstract
Mammary tumorigenesis is associated with the increased expression of several proteins in the focal adhesion complex, including focal adhesion kinase (FAK) and various integrins. Aberrant expression of these molecules occurs concomitant with the conversion of TGF-β function from a tumor suppressor to a tumor promoter. We previously showed that interaction between β3 integrin and TβR-II facilitates TGF-β-mediated oncogenic signaling, epithelial-mesenchymal transition (EMT), and metastasis. However, the molecular mechanisms by which the focal adhesion complex contributes to β3 integrin:TβR-II signaling and the oncogenic conversion of TGF-β remain poorly understood.Keywords
This publication has 48 references indexed in Scilit:
- Integrin β 1 -focal adhesion kinase signaling directs the proliferation of metastatic cancer cells disseminated in the lungsProceedings of the National Academy of Sciences, 2009
- TRAF6 Mediates Smad-Independent Activation of JNK and p38 by TGF-βMolecular Cell, 2008
- Grb2 binding to Tyr284 in TβR-II is essential for mammary tumor growth and metastasis stimulated by TGF-βCarcinogenesis: Integrative Cancer Research, 2008
- Nuclear FAK Promotes Cell Proliferation and Survival through FERM-Enhanced p53 DegradationMolecular Cell, 2008
- Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progressionProceedings of the National Academy of Sciences of the United States of America, 2007
- Distinct FAK-Src activation events promote α5β1 and α4β1 integrin-stimulated neuroblastoma cell motilityOncogene, 2007
- FAK Is Required for TGFβ-induced JNK Phosphorylation in Fibroblasts: Implications for Acquisition of a Matrix-remodeling PhenotypeMolecular Biology of the Cell, 2007
- Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesisBreast Cancer Research and Treatment, 2004
- TGF-β signaling: positive and negative effects on tumorigenesisCurrent Opinion in Genetics & Development, 2002
- Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient miceNature, 1995