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Periostin, a Cell Adhesion Molecule, Facilitates Invasion in the Tumor Microenvironment and Annotates a Novel Tumor-Invasive Signature in Esophageal Cancer
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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. ©2010 AACR.
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“Michaylira et al . 67 used 3D cell culture techniques to find that another cell adhesion molecule, periostin, which boosts the invasiveness of esophageal tumors, could be useful in search for new therapeutic targets for esophageal cancer.”
From Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors (2014) · cites this paper as [67]
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Metadata
- Authors
- Michaylira, C. Z., Wong, G. S., Miller, C. G., Gutierrez, C. M., Nakagawa, H., Hammond, R., Klein-Szanto, A. J., Lee, J.-S., Kim, S. B., Herlyn, M., Diehl, J. A., Gimotty, P., & Rustgi, A. K.
- Affiliations
- The Wistar Institute (US)
- Authors' Affiliations: 1Division of Gastroenterology, Departments of 2Medicine, 3Genetics, and 4Cancer Biology, 5Abramson Cancer Center, and 6Division of Biostatistics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; 7Division of Basic Science, Tumor Cell Biology, Fox Chase Cancer Center; and 8Wistar Institute, Philadelphia, Pennsylvania; and 9Departent of Systems Biology, M.D. Anderson Cancer Center, Houston, Texas
- Corresponding author
- Rustgi, Anil K.
- Venue
- Cancer Research
- Published
- 2010-06-30
- Volume
- 70
- Issue
- 13
- Pages
- 5281-5292
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3274349
- OpenAlex
- W2123522555
- Cited by
- 117
- References
- 34
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 9 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 11 · 2013: 13 · 2012: 8
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Cancer Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P01CA098101, T32CA115299, P30CA016520)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK075230, P30DK050306)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Keywords
- periostin, esophageal squamous cell carcinoma, tumor invasion, tumor microenvironment, adhesion molecules, organotypic culture, tumor cell migration, epidermal growth factor receptor signaling, p53, metastasis
- MeSH terms
- Carcinoma, Squamous Cell, Esophageal Neoplasms, Humans, Neoplasm Invasiveness, Tumor Cells, Cultured, Cell Adhesion Molecules, Tumor Suppressor Protein p53, Telomerase, Gene Expression Profiling, ErbB Receptors
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