Epithelial–mesenchymal transition to mitigate age-related progression in lung cancer

IF 12.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2024-11-07 DOI:10.1016/j.arr.2024.102576

Riya Thapa , Saurabh Gupta , Gaurav Gupta , Asif Ahmad Bhat , Smriti , Madhav Singla , Haider Ali , Sachin Kumar Singh , Kamal Dua , Manoj Kumar Kashyap

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Abstract

Epithelial–Mesenchymal Transition (EMT) is a fundamental biological process involved in embryonic development, wound healing, and cancer progression. In lung cancer, EMT is a key regulator of invasion and metastasis, significantly contributing to the fatal progression of the disease. Age-related factors such as cellular senescence, chronic inflammation, and epigenetic alterations exacerbate EMT, accelerating lung cancer development in the elderly. This review describes the complex mechanism among EMT and age-related pathways, highlighting key regulators such as TGF-β, WNT/β-catenin, NOTCH, and Hedgehog signalling. We also discuss the mechanisms by which oxidative stress, mediated through pathways involving NRF2 and ROS, telomere attrition, regulated by telomerase activity and shelterin complex, and immune system dysregulation, driven by alterations in cytokine profiles and immune cell senescence, upregulate or downregulate EMT induction. Additionally, we highlighted pathways of transcription such as SNAIL, TWIST, ZEB, SIRT1, TP53, NF-κB, and miRNAs regulating these processes. Understanding these mechanisms, we highlight potential therapeutic interventions targeting these critical molecules and pathways.

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上皮-间充质转化缓解肺癌与年龄相关的进展。

上皮-间质转化（EMT）是胚胎发育、伤口愈合和癌症进展过程中的一个基本生物学过程。在肺癌中，EMT 是侵袭和转移的关键调节因子，是导致病情恶化的重要因素。与年龄有关的因素，如细胞衰老、慢性炎症和表观遗传学改变会加剧 EMT，从而加速老年肺癌的发展。本综述描述了 EMT 与年龄相关途径之间的复杂机制，重点介绍了 TGF-β、WNT/β-catenin、NOTCH 和刺猬信号等关键调控因子。我们还讨论了氧化应激（通过涉及 NRF2 和 ROS 的途径介导）、端粒消减（由端粒酶活性和庇护素复合物调节）以及免疫系统失调（由细胞因子谱改变和免疫细胞衰老驱动）上调或下调 EMT 诱导的机制。此外，我们还强调了调控这些过程的转录途径，如 SNAIL、TWIST、ZEB、SIRT1、TP53、NF-κB 和 miRNA。了解了这些机制后，我们重点介绍了针对这些关键分子和通路的潜在治疗干预措施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.