NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a β2AR-Akt feedback loop that activates autophagy.
NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a β2AR-Akt feedback loop that activates autophagy.
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DOI：
10.1002/1878-0261.13230
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发表时间：
2022-08
影响因子：
6.6
通讯作者：
Wang, Zheng
中科院分区：
文献类型：
--
作者：
Chen, Xin;Zhang, Weifan;Liu, Rujuan;Zhu, Zeen;Gong, Mengyuan;Wang, Qiqi;Qian, Weikun;Wu, Zheng;Ma, Qingyong;Wang, Zheng
Low responsiveness to chemotherapy is an important cause of poor prognosis in pancreatic cancer. Smoking is a high‐risk factor for pancreatic cancer and cancer resistance to gemcitabine; however, the underlying mechanisms remain unclear. 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) is the main metabolite of tobacco burning and has been shown to be associated with cancer development and chemoresistance. However, in pancreatic cancer, its mechanism remains poorly understood. In this study, we found that NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Moreover, NNK increased autophagy and elevated the expression levels of the autophagy‐related markers autophagy‐related gene 5 (ATG5), autophagy‐related gene 7 (ATG7), and Beclin1. Furthermore, the results showed that NNK‐promoted stemness and gemcitabine resistance was partially dependent on the role of NNK in cell autophagy, which is mediated by the β2‐adrenergic receptor (β2AR)‐Akt axis. Finally, we proved that NNK intervention could not only activate β2AR, but also increase its expression, making β2AR and Akt form a feedback loop. Overall, these findings show that the NNK‐induced β2AR‐Akt feedback loop promotes stemness and gemcitabine resistance in pancreatic cancer cells. β2AR, activated by NNK, increases Akt activity and further promotes autophagy, which leads to the formation of stemness and gemcitabine resistance of pancreatic cancer cells. Activation of Akt or downstream signals can increase β2AR expression in a feedback loop.
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DOI：
10.1016/j.bbadis.2010.07.003
发表时间：
2011-01-01
影响因子：
6.2
作者：
Aranguiz-Urroz, Pablo;Canales, Jimena;Diaz-Araya, Guillermo
通讯作者：
Diaz-Araya, Guillermo
影响因子：
29.4
作者：
Nimmakayala RK;Seshacharyulu P;Lakshmanan I;Rachagani S;Chugh S;Karmakar S;Rauth S;Vengoji R;Atri P;Talmon GA;Lele SM;Smith LM;Thapa I;Bastola D;Ouellette MM;Batra SK;Ponnusamy MP
通讯作者：
Ponnusamy MP
影响因子：
8.4
作者：
Gordon, William;Galitovskiy, Valentin;Grando, Sergei A.
通讯作者：
Grando, Sergei A.
影响因子：
2.9
作者：
Pham H;Chen M;Takahashi H;King J;Reber HA;Hines OJ;Pandol S;Eibl G
通讯作者：
Eibl G
影响因子：
8.8
作者：
Piffoux M;Eriau E;Cassier PA
通讯作者：
Cassier PA