Periostin, a cell adhesion molecule, facilitates invasion in the tumor microenvironment and annotates a novel tumor-invasive signature in esophageal cancer.
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.
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Carmen Z
CZ
Michaylira
Gabrielle S
GS
Wong
Charles G
CG
Miller
Christie M
CM
Gutierrez
Hiroshi
H
Nakagawa
Rachel
R
Hammond
Andres J
AJ
Klein-Szanto
Ju-Seog
JS
Lee
Sang Bae
SB
Kim
Meenhard
M
Herlyn
J Alan
JA
Diehl
Phyllis
P
Gimotty
Anil K
AK
Rustgi
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D009361:Neoplasm Invasiveness; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; C509186:TERT protein, human; D019098:Telomerase