Targeting the p53-p21 axis in liver cancer: Linking cellular senescence to tumor suppression and progression

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2024-10-15 DOI:10.1016/j.prp.2024.155652

Lakshmi Thangavelu , Abdulmalik S.A. Altamimi , Nehmat Ghaboura , M. Arockia Babu , R. Roopashree , Pawan Sharma , Pusparghya Pal , Chhavi Choudhary , G.V. Siva Prasad , Aashna Sinha , Ashok Kumar Balaraman , Sushama Rawat

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引用次数: 0

Abstract

Liver cancer is a major health epidemic worldwide, mainly due to its high mortality rates and limited treatment options. The association of cellular senescence to tumorigenesis and the cancer hallmarks remains a subject of interest in cancer biology. The p53-p21 signalling axis is an important regulator in restoring the cell’s balance by supporting tumor suppression and tumorigenesis in liver cancer. We review the novel molecular mechanisms that p53 and its downstream effector, p21, employ to induce cellular senescence, making it last longer, and halt the proliferation of damaged hepatocytes to become tumorous cells. We also examine how dysregulation of this pathway contributes to HCC pathogenesis, proliferation, survival, acquired resistance to apoptosis, and increased invasiveness. Furthermore, we comprehensively describe the molecular cross-talk between the p53-p21 signalling axis and major cell cycle signalling pathways, including Wnt/β-catenin, PI3K/Akt, and TGF-β in liver cancer and provide an overview of promising candidates for chemoprevention and future therapeutic strategies. This review article explores the roles of the p53-p21 pathway in liver cancer, examining its function in promoting cellular senescence under normal conditions and its potential role in cancer progression. It also highlights novel therapeutic drugs and drug targets within the pathway and discusses the implications for treatment strategies and prognosis in liver cancer.

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针对肝癌中的 p53-p21 轴：将细胞衰老与肿瘤抑制和进展联系起来

肝癌是世界范围内的一种主要流行病，这主要是由于肝癌的高死亡率和有限的治疗方案造成的。细胞衰老与肿瘤发生和癌症特征之间的关系仍然是癌症生物学中一个令人感兴趣的课题。p53-p21 信号轴是恢复细胞平衡的重要调节器，它支持肝癌中的肿瘤抑制和肿瘤发生。我们回顾了 p53 及其下游效应物 p21 在诱导细胞衰老、延长衰老时间以及阻止受损肝细胞增殖成为肿瘤细胞方面所采用的新型分子机制。我们还研究了这一途径的失调是如何导致 HCC 发病、增殖、存活、获得性抗凋亡和侵袭性增加的。此外，我们还全面描述了肝癌中 p53-p21 信号轴与主要细胞周期信号通路（包括 Wnt/β-catenin、PI3K/Akt 和 TGF-β）之间的分子交叉对话，并概述了化学预防和未来治疗策略的候选方案。这篇综述文章探讨了 p53-p21 通路在肝癌中的作用，研究了它在正常情况下促进细胞衰老的功能及其在癌症进展中的潜在作用。文章还重点介绍了该通路中的新型治疗药物和药物靶点，并讨论了其对肝癌治疗策略和预后的影响。

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

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.