ArticleCell cycle (Georgetown, Tex.)2013
Cigarette smoke metabolically promotes cancer, via autophagy and premature aging in the host stromal microenvironment.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Cigarette smoking and the risk of nasopharyngeal carcinoma: a meta-analysis of epidemiological studies.BMJ open · 2017Pooled it
- Environmental tobacco smoking (ETS) and esophageal cancer: A population-based case-control study in Jiangsu Province, China.International journal of cancer · 2025Article
- Mitophagy in health and disease. Molecular mechanisms, regulatory pathways, and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2024Review
- Intra-Parotid Recurrent Nasopharyngeal Carcinoma Following Intensity-Modulated Radiation Therapy: A Case Report.Clinical medicine insights. Case reports · 2024Article
- β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells.Biomedicines · 2022Article
- Key promoters of tumor hallmarks.International journal of clinical oncology · 2022Review
- The role of cancer stromal fibroblasts in mediating the effects of tobacco-induced cancer cell growth.Cancer cell international · 2021Review
- Nuclear factor kappa-B contributes to cigarette smoke tolerance in pancreatic ductal adenocarcinoma through cysteine metabolism.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Rethinking carcinogenesis: The detached pericyte hypothesis.Medical hypotheses · 2020Article
- Effects of Inhaled Tobacco Smoke on the Pulmonary Tumor Microenvironment.Advances in experimental medicine and biology · 2020Review
- Vasorin/ATIA Promotes Cigarette Smoke-Induced Transformation of Human Bronchial Epithelial Cells by Suppressing Autophagy-Mediated Apoptosis.Translational oncology · 2020Article
- Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma.Molecular cancer research : MCR · 2019Article
- Blood Cadmium Level Is Associated with Short Progression-Free Survival in Nasopharyngeal Carcinoma.International journal of environmental research and public health · 2019Article
- Joint effect of smoking and NQO1 C609T polymorphism on undifferentiated nasopharyngeal carcinoma risk in a North African population.Molecular genetics & genomic medicine · 2018Article
- Tobacco Use and Effects of Professional Advice on Smoking Cessation among Youth in IndiaAsian Pacific journal of cancer prevention : APJCP · 2017Article
- Functional Effects of Cigarette Smoke-Induced Changes in Airway Smooth Muscle Mitochondrial Morphology.Journal of cellular physiology · 2017Article
- On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer.Oncotarget · 2016Review
- Nicotine Reduces Survival via Augmentation of Paracrine HGF-MET Signaling in the Pancreatic Cancer Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways.Cell death & disease · 2015Article
- Cigarette smoke exposure triggers the autophagic cascade via activation of the AMPK pathway in mice.Biology of reproduction · 2015Article
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 6 countries.
Funding
Abstract
Cigarette smoke has been directly implicated in the disease pathogenesis of a plethora of different human cancer subtypes, including breast cancers. The prevailing view is that cigarette smoke acts as a mutagen and DNA damaging agent in normal epithelial cells, driving tumor initiation. However, its potential negative metabolic effects on the normal stromal microenvironment have been largely ignored. Here, we propose a new mechanism by which carcinogen-rich cigarette smoke may promote cancer growth, by metabolically "fertilizing" the host microenvironment. More specifically, we show that cigarette smoke exposure is indeed sufficient to drive the onset of the cancer-associated fibroblast phenotype via the induction of DNA damage, autophagy and mitophagy in the tumor stroma. In turn, cigarette smoke exposure induces premature aging and mitochondrial dysfunction in stromal fibroblasts, leading to the secretion of high-energy mitochondrial fuels, such as L-lactate and ketone bodies. Hence, cigarette smoke induces catabolism in the local microenvironment, directly fueling oxidative mitochondrial metabolism (OXPHOS) in neighboring epithelial cancer cells, actively promoting anabolic tumor growth. Remarkably, these autophagic-senescent fibroblasts increased breast cancer tumor growth in vivo by up to 4-fold. Importantly, we show that cigarette smoke-induced metabolic reprogramming of the fibroblastic stroma occurs independently of tumor neo-angiogenesis. We discuss the possible implications of our current findings for the prevention of aging-associated human diseases and, especially, common epithelial cancers, as we show that cigarette smoke can systemically accelerate aging in the host microenvironment. Finally, our current findings are consistent with the idea that cigarette smoke induces the "reverse Warburg effect," thereby fueling "two-compartment tumor metabolism" and oxidative mitochondrial metabolism in epithelial cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.