title: NOS1S-nitrosylates PTEN and inhibits autophagy in nasopharyngeal carcinoma cells.
abstract: Autophagy is a cellular survival mechanism that involves the catabolic degradation of damaged proteins and organelles during periods of metabolic stress, and when overly stimulated, commonly contributes to cell death. Nitric oxide (NO), a potent cellular messenger, participates in a complex mechanism which assists in controlling autophagy. However, the mechanism by which endogenous NO formed by distinct isoforms of nitric oxide synthase (NOS) helps to regulate autophagy in cancer cells remains unclear. Here we report that NOS1 reduces excessive levels of autophagy and promotes the survival of nasopharyngeal carcinoma cells. We found that inhibition of NOS1 increased cell death resulting from siRNA or the use of pharmacologic agents; and this effect was reversed by the autophagy inhibitor, chloroquine. The role of NOS1 in the autophagy process depended on the activation of AKT/mTOR signaling byS-nitrosylation of phosphatase and tensin homolog (PTEN) proteins. The mechanism by which NOS1 modifies PTEN protein might involve a direct interaction between these two molecules. Moreover, in anin vivostudy, the NOS1 inhibitor N(G)-nitro-L-arginine methyl ester activated AKT/mTOR signaling and promoted autophagy in xenograph tumors. Our studies demonstrated that NOS1 prevents excessive autophagy viaS-nitrosylation of PTEN, and activation of the AKT/mTOR signaling pathway. PTEN and the AKT/mTOR signaling pathway are promising targets for improving the chemotherapeutic treatment of cancer.
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Lingqun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Qianbing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Bingtao
authors.initials: B
authors.lastname: Hao
authors.affiliation: Sidra Medical and Research Center, Out-Patient Clinic , PO Box 26999, Al Luqta Street, Education City North Campus, Qatar Foundation, Doha, Qatar.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.affiliation: Department of Vascular Surgery, Nanfang Hospital Southern Medical University , Guangzhou, China.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Qianli
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Keyi
authors.initials: K
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Gao
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Kaitai
authors.initials: K
authors.lastname: Yao
authors.affiliation: Cancer Research Institute, Southern Medical University , Guangzhou, China.
authors.forename: Qiuzhen
authors.initials: Q
authors.lastname: Liu