Molecular Mechanisms Linking E‑cigarette Exposure to Cancer Metastatic Behaviour: Focus on Epithelial-to-Mesenchymal Transition and Inflammation: A Systematic Review

Abstract

Electronic cigarette use has been mushrooming globally in recent years, with an estimated 82 million vapers worldwide, including 14.3 million in Southeast Asia. Although e-cigarettes are generally considered a safer alternative to traditional cigarettes, their long-term health effects, particularly on cancer progression and metastasis, remain uncertain. This systematic review evaluated the existing literature to determine whether e-cigarette exposure influences cancer cell metastatic behaviour. A systematic search was conducted using predefined terms in MEDLINE, PubMed, and Web of Science from database inception to 1^st May 2025. The studies must be primary research and investigate the effects of e-cigarette exposure on cancer cell metastasis. Seven eligible studies were selected, assessed for reliability using the SciRAP tool, and synthesised manually. The literature evaluated several aspects of cancer metastasis, including cell invasion, migration and motility, morphological changes, tumour area, growth, proliferation, colonisation or localisation, cell viability, and immunological changes. Evidence synthesis suggests that e-cigarette exposure may promote cancer cell migration; however, these findings are constrained by the small number of studies, methodological limitations, and lack of long-term investigations. Reported effects varied depending on cancer cell type, nicotine presence, and e-liquid flavouring. Current preclinical data indicate e-cigarette exposure may promote cancer metastatic behaviour through epithelial-to-mesenchymal transition (EMT) induction (E-cadherin loss, vimentin upregulation), RAGE-mediated inflammatory signalling, and CCL5/CCR5-dependent monocyte recruitment. However, all seven included studies were rated “not reliable” by SciRAP (methodological quality scores 47–70%), rendering evidence preliminary.  Future studies require physiologically relevant direct aerosol exposure systems, cigarette smoke comparators for relative risk assessment, diverse cancer models, and longitudinal clinical investigations to establish the true impact of vaping on cancer metastasis.