Nestin regulates proliferation, migration, invasion and stemness of lung adenocarcinoma

Abstract

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.

Inhibition of nestin suppresses stem cell phenotype of glioblastomas through the alteration of post-translational modification of heat shock protein HSPA8/HSC71

“…Our previous studies have shown that nestin regulates the sphere formation ability of glioblastomas, melanomas, lung adenocarcinomas, and pancreatic cancer [23][24][25]. In this study, nestin was detected in perivascular and perinecrostic lesions, which are considered a niche for BTSCs.…”

“…We have also shown that knockdown of nestin expression suppresses migration, invasion, and sphere formation in pancreatic cancer [22,23], malignant melanomas [24] and lung cancer [25]. Similarly, Lu et al demonstrated that blocking the expression of nestin in glioblastomas by intratumoral injection of shRNA significantly reduced tumor growth and volume [19].…”

Clinical significance of nestin and its association with survival in neuroendocrine lung tumours

“…Nestin expression in tumour samples positively correlated with tumour size, lymph node metastasis and there was negative association with survival. On cell lines, it corresponded with increased proliferation, migration and invasion capacities [25]. Basing on our results and presented studies, nestin detection may serve in the future, as a biomarker used to predict prognosis and facilitate patient-oriented approach to treatment.…”

“…When it comes to nestin and other lung malignancies, it was identified as CSC marker in non-small cell lung cancer (NSCLC) [24]. Narita et al found nestin on immunohistochemical analysis performed on surgical specimens of NSCLC [25].…”

Nestin expression as an independent indicator of poor prognosis for patients with anaplastic thyroid cancer

“…The acceleration of cancer cell proliferation, invasive growth and migration have previously been reported to correlate with nestin expression in several cancer types (22)(23)(24). These features are cellular mechanisms underlying cancer progression and metastasis, and they are also common characteristics found in ATC cells.…”