Lung cancer is the most common
cancer and the most common cause of
cancer-related death in the world.
Nestin, a class VI intermediate filament, is known to be a cancer stem cell (CSC) marker as well as a neuroepithelial stem cell marker. High expression levels of
nestin are reported in several types of
cancers including lung, pancreatic and
prostate cancers.
Nestin is thought to regulate
tumor cell proliferation, migration, invasion and CSC properties. Here, we confirmed
nestin expression in
non-small cell lung cancer (NSCLC): Immunohistochemical analysis in surgical specimens detected
nestin protein expression in the cytoplasm of 20 of 48
adenocarcinoma (AD) cases (41.7%) and 25 of 47
squamous cell carcinoma cases (53.2%).
Nestin immunoreactivity significantly correlated with not only
tumor size and
lymph node metastasis in NSCLC, but also poor survival in surgical patients with AD. High and moderate expression levels of
nestin were confirmed in several lung AD cell lines including H1975 and PC-3.
Nestin inhibition by
shRNA decreased proliferation, migration, invasion and sphere formation in AD cells. Correspondingly,
nestin upregulation by
nestin gene transfection resulted in the opposite changes. Moreover,
Akt inhibitor IV effectively decreased
nestin expression via SRY-box containing
protein 2 (Sox2) downregulation and overcame the enhanced sphere formation induced by
nestin upregulation. Overall, our results show that
nestin correlates with the aggressiveness and stemness of AD. Regulation of
nestin via Akt/Sox2 is, thus, a promising candidate for novel therapeutic approaches to eradicate CSCs in lung AD.