EphA2 induction of fibronectin creates a permissive microenvironment for malignant cells

Min Hu, Kelly L. Carles-Kinch, Daniel P. Zelinski, Michael S. Kinch

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Normal and metastatic cells continuously exchange information with the surrounding tissue environment, and this communication governs many aspects of cell behavior. In particular, the physical placement or adhesions of cells within their environment are increasingly understood to facilitate this communication. Classically, cell-cell and cell-extracellular matrix adhesions have been viewed as separable events that are independently controlled. This simple view is changing, as evidence emerges of coordinated regulation of cellular adhesions. Here, we show that the EphA2 tyrosine kinase, which is overexpressed in many aggressive cancers, regulates a fine balance of cell-cell and cell-extracellular matrix adhesions in epithelial cells. EphA2 selectively inhibits cell-cell adhesions by increasing cell attachment and up-regulating the extracellular matrix protein fibronectin. We also show that fibronectin can contribute to important aspects of malignant character. Antibody-based targeting of EphA2 inhibits malignant cell growth by decreasing fibronectin and thereby inducing apoptotic death. Our findings strengthen a concept that cancer progression is regulated by a bidirectional communication between tumor cells and their surrounding microenvironment.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalMolecular Cancer Research
Issue number10
StatePublished - Oct 1 2004


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