Title:Radiation-Induced Pulmonary Epithelial-Mesenchymal Transition: A Review on Targeting Molecular Pathways and Mediators
VOLUME: 19 ISSUE: 10
Author(s):Sunilgowda Sunnaghatta Nagaraja and Devipriya Nagarajan*
Affiliation:Radiation biology lab, Anusandhan Kendra - II, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil nadu, Radiation biology lab, Anusandhan Kendra - II, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil nadu
Keywords:Radiation, EMT, epigenetics, inhibitors, fibrosis, signaling pathways.
Abstract:Background: Radiotherapy is the most widely used treatment method for average and advanced
lung cancer patients. Moreover, the clinical toxicities caused by radiotherapy are categorized
into acute radiation pneumonitis and late pulmonary fibrosis. Epithelial-mesenchymal transition
(EMT) is a complex physiological process involves many signaling molecules and proteins like adaptor
proteins, and transcriptional factors. It was identified as a significant mechanism for fibrosis,
wound healing and also cancer. A variety of biomarkers have appeared in radiation-induced lung
EMT, some of which are acquired (N-cadherin, vimentin and fibronectin, etc.) and some of which are
repressed during the transition of epithelial cells (E-cadherin, zona occludens-1).
Objective: In the current review, we highlighted the radiation-induced lung EMT signaling pathway
and their mediators. We also discuss the EMT in cancer, fibrosis and its epigentics.
Results: Radiation-induced lung EMT is controlled by numerous signaling pathways like MAPK, NF-
κB, Wnt, microRNAs and histone modifications. Transcriptional factors such as Snail, slug, twist,
ZEB1 (Zinc finger E-box binding-1) and ZEB2 (Zinc finger E-box binding-2) proteins are inducers
linking radiation-induced EMT and fibrosis. Epigenetic modulations are heritable changes in the structure
and function of the genome that occurs without any change in the sequence. Several approaches
showed the role of epigenetic modifications and its inhibitors in controlling fibrosis and cancer. Only
limited reports are focused on understanding the epigenetic regulations of radiation-induced lung
EMT.
Conclusion: The current review focused on recent findings regarding radiation-induced lung fibrosis
and EMT, thus provides some information on important signaling pathways, its subsequent expression
of genes and proteins involved in EMT. This review also discussed various inhibitors that could be
used to treat EMT related diseases, i.e., fibrosis, cancer.
