Periostin (POSTN, PN, or osteoblast-specific factor OSF-2) is a multifunctional
cytokine that signals between the cell and the extracellular matrix. Periostin plays
an important role in tumor development and is involved in carcinoma cell epithelialmesenchymal
transition (EMT), whereby mature epithelial cells undergo phenotypic
morphological changes and become invasive, motile cells. Here, we discuss the
molecular mechanisms involved in periostin-induced promotion of EMT in lung cancer
cells. Online TCGA datasets demonstrate the prognostic relevance of periostin in lung
cancer; a higher periostin level correlates with poor overall survival. Similarly, our
IHC results show that high periostin expression is positively correlated with the EMT
markers Snail and Twist, as well as stage of lung cancer. We found that recombinant
periostin induces the EMT phenotype in lung cancer cells through the p38/ERK pathway,
while pretreatment with chemical inhibitors prevented periostin-induced EMT induction.
Moreover, we found that periostin regulates EMT by repressing microRNA-381 (miR-
381) expression, which targets both Snail and Twist. Using the miR-381 mimic, we
dramatically reversed periostin-induced Snail and Twist expression. Furthermore,
periostin knockdown dramatically affected EMT markers and cell migration potential.
The role of periostin in lung cancer progression is elucidated by the in vivo mouse
model. Our findings indicate that changes in periostin expression in lung cancer may
serve as a therapeutic target for the treatment of lung cancer metastasis.