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View the Table of Contents for the February 15 issue of Clinical Cancer Research.
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Merchant et al. Page 1182 TNF-α converting enzyme (TACE) has been implicated in the cleavage of the epidermal growth factor receptor (EGFR) ligands transforming growth factor-α (TGF-α) and amphiregulin at the cell surface. Here, Merchant and colleagues show in a polarizing colorectal cancer (CRC) cell line that TACE, TGF-α, amphiregulin, and EGFR all localize to the basolateral cell surface, and they describe the spatial compartmentalization of these components as the EGFR axis. They found that TACE is overexpressed in primary and metastatic CRC tumors compared with normal colonic mucosa and that its expression is inversely correlated to that of TGF-α and amphiregulin. Furthermore, pharmacologic blockade using a monoclonal antibody against EGFR, a tyrosine kinase inhibitor, and a selective TACE inhibitor resulted in cooperative growth inhibition and increased apoptosis, implicating TACE as a promising target for EGFR axis inhibition in CRC.
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