Abstract
BackgroundNestin is associated with neoplastic transformation, but the mechanisms by which nestin contributes to invasion and malignancy of lung cancer remain unknown. Considering that proliferation is necessary for malignant behavior, we investigated the mechanism of nestin action in association with the proliferative properties of non-small cell lung cancer (NSCLC).MethodsNestin expression was examined in NSCLC specimens and cell lines. Associations with clinicopathological features, including prognosis and proliferative markers, were evaluated. Effects of nestin knockdown on proliferation and the signaling pathways involved were further investigated.ResultsNestin was expressed in most cancer specimens and all the tumor cell lines analyzed. High nestin expression in malignant tissue was associated with high Ki-67 or PCNA levels and poor patient outcomes. Conversely, knockdown of nestin expression led to significant inhibition of tumor cell proliferation, decreased colony forming ability, and cell cycle G1 arrest. Furthermore, nestin knockdown resulted in inhibition of Akt and GSK3β activation.ConclusionsOur data demonstrate that nestin expression in NSCLC cells is associated with poor prognosis of patients and tumor cell proliferation pathway. Downregulation of nestin efficiently inhibited lung cancer cell proliferation, which might be through affecting cell cycle arrest and Akt-GSK3β-Rb signaling pathway.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide
To determine whether tumor cell proliferative inhibition is related to cell cycle regulation, we investigated the effects of nestin knockdown on cell cycle progression in cancer cells
We showed that nestin expression is significantly associated with malignant features of non-small cell lung cancer (NSCLC) tissue, poorly differentiated phenotype and histology classification
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide. In non-small cell lung cancer (NSCLC), which accounts for 80% of all lung cancer cases, distant metastases develop in up to 70% of patients with early-stage disease [1,2]. Malignant features of NSCLC involve several important events, including proliferation and invasion of primary tumor, sustained angiogenesis, and evasion of apoptosis. Proliferation of primary tumor is an integral part of molecular and cellular pathogenesis, development, and metastasis of lung cancer [4]. Nestin is associated with neoplastic transformation, but the mechanisms by which nestin contributes to invasion and malignancy of lung cancer remain unknown. Considering that proliferation is necessary for malignant behavior, we investigated the mechanism of nestin action in association with the proliferative properties of non-small cell lung cancer (NSCLC)
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