ArticleMolecular oncology2022
NNK from tobacco smoking enhances pancreatic cancer cell stemness and chemoresistance by creating a β2AR-Akt feedback loop that activates autophagy.
Article in Molecular oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 10 papers.
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10 citing papers in PubMed, 22 citations in OpenAlex.
- Integrative multi-omics and radiogenomic profiling decodes NNK-related tumor remodeling and prognostic stratification in pancreatic cancer.International journal of surgery (London, England) · 2026Article
- Article
- Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer.World journal of gastroenterology · 2025Article
- Tobacco carcinogen NNK promotes pancreatic cancer proliferation via LINC00857/β-catenin.Tobacco induced diseases · 2025Article
- Microbiome and metabolome analysis in smoking and non-smoking pancreatic ductal adenocarcinoma patients.BMC microbiology · 2024Article
- PI3K/AKT Immunoexpression Influences the Prognostic Factors of Patients Diagnosed with Oropharyngeal Squamous Cell Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- miRNA signatures underlie chemoresistance in the gemcitabine-resistant pancreatic ductal adenocarcinoma cell line MIA PaCa-2 GR.Frontiers in genetics · 2024Article
- Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.Neuroscience bulletin · 2023Review
- Epidemiology of pancreatic cancer: New version, new vision.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2023Article
- Smoking induces WEE1 expression to promote docetaxel resistance in esophageal adenocarcinoma.Molecular therapy oncolytics · 2023Article
Corrections and comments
- Retracted
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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