Cigarette Smoke-Induced Epithelial-to-Mesenchymal Transition: Insights into Cellular Mechanisms and Signaling Pathways

Abstract

This review delves into the molecular complexities underpinning the epithelial-to-mesenchymal transition (EMT) induced by cigarette smoke (CS) in human bronchial epithelial cells (HBECs). The complex interplay of pathways, including those related to WNT//β-catenin, TGF-β/SMAD, hypoxia, oxidative stress, PI3K/Akt, and NF-κB, plays a central role in mediating this transition. While these findings significantly broaden our understanding of CS-induced EMT, the research reviewed herein leans heavily on 2D cell cultures, highlighting a research gap. Furthermore, the review identifies a stark omission of genetic and epigenetic factors in recent studies. Despite these shortcomings, the findings furnish a consolidated foundation not only for the academic community but also for the broader scientific and industrial sectors, including large tobacco companies and manufacturers of related products, both highlighting areas of current understanding and identifying areas for deeper exploration. The synthesis herein aims to propel further research, hoping to unravel the complexities of the EMT in the context of CS exposure. This review not only expands our understanding of CS-induced EMT but also reveals critical limitations in current methodologies, primarily the reliance on 2D cell cultures, which may not adequately simulate more complex biological interactions. Additionally, it highlights a significant gap in the literature concerning the genetic and epigenetic factors involved in CS-induced EMT, suggesting an urgent need for comprehensive studies that incorporate these types of experiments.

Keywords: 2D cell cultures; EMT; cigarette smoke; epithelial-to-mesenchymal transition; normal human bronchial cell.

Figure 1

Immortalized HBECs after exposure to CS: potential pathological consequences and involved signaling pathways.

Figure 2

Comparative overview of cellular environments: 2D vs. 3D cultures in the study of EMT.