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Michaylira CZ , Wong GS , Miller CG , Gutierrez CM , Nakagawa H , Hammond R , Klein-Szanto AJ , Lee JS , Kim SB , Herlyn M , Diehl JA , Gimotty P , Rustgi AK
Periostin, a Cell Adhesion Molecule, Facilitates Invasion in the Tumor Microenvironment and Annotates a Novel Tumor-Invasive Signature in Esophageal Cancer
Cancer Research. 2010 Jul;70(13) :5281-5292
PMCID: PMC3274349   
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Abstract
Human squamous cell cancers are the most common epithelially derived malignancies. One example is esophageal squamous cell carcinoma (ESCC), which is associated with a high mortality rate that is related to a propensity for invasion and metastasis. Here, we report that periostin, a highly expressed cell adhesion molecule, is a key component of a novel tumor-invasive signature obtained from an organotypic culture model of engineered ESCC. This tumor-invasive signature classifies with human ESCC microarrays, underscoring its utility in human cancer. Genetic modulation of periostin promotes tumor cell migration and invasion as revealed in gain-of-loss and loss-of-function experiments. Inhibition of epidermal growth factor receptor signaling and restoration of wild-type p53 function were each found to attenuate periostin, suggesting the interdependence of two common genetic alterations with periostin function. Collectively, our studies reveal periostin as an important mediator of ESCC tumor invasion and they indicate that organotypic (three-dimensional) culture can offer an important tool to discover novel biological effectors in cancer. Cancer Res; 70(13); 5281-92. (C) 2010 AACR.
Notes
Michaylira, Carmen Z. Wong, Gabrielle S. Miller, Charles G. Gutierrez, Christie M. Nakagawa, Hiroshi Hammond, Rachel Klein-Szanto, Andres J. Lee, Ju-Seog Kim, Sang Bae Herlyn, Meenhard Diehl, J. Alan Gimotty, Phyllis Rustgi, Anil K. Amer assoc cancer research Philadelphia 618zy