Neuroendocrine (NE) phenotypes characterize a spectrum of lung tumors, including 
low-grade typical and intermediate-grade atypical carcinoid, high-grade 
large-cell NE carcinoma and small cell lung carcinoma. Currently, no effective 
treatments are available to cure NE lung tumors, demanding identification of 
biological features specific to these tumors. Here, we report that autophagy has 
an important role for NE lung tumor cell proliferation and survival. We found 
that the expression levels of the autophagy marker LC3 are relatively high in a 
panel of lung tumor cell lines expressing high levels of neuron-specific enolase 
(NSE), a key NE marker in lung tumors. In response to bafilomycin A1 and 
chloroquine, NE lung tumor cells exhibited cytotoxicity whereas non-NE lung 
tumor cells exhibited cytostasis, indicating a distinct role of autophagy for NE 
lung tumor cell survival. Intriguingly, in certain NE lung tumor cell lines, the 
levels of processed LC3 (LC3-II) were inversely correlated with AKT activity. 
When AKT activity was inhibited using AKTi or MK2206, the levels of LC3-II and 
SQSTM1/p62 were increased. In contrast, torin 1, rapamycin or mTOR knockdown 
increased p62 levels, suggesting that these two pathways have opposing effects 
on autophagy in certain NE lung tumors. Moreover, inhibition of one pathway 
resulted in reduced activity of the other, suggesting that these two pathways 
crosstalk in the tumors. These results suggest that NE lung tumor cells share a 
common feature of autophagy and are more sensitive to autophagy inhibition than 
non-NE lung tumor cells.