Intricate effects of post-translational modifications in liver cancer: mechanisms to clinical applications

Zhang, Yu; Xu, Weihao; Peng, Chuanhui; Ren, Shenli; Zhang, Cheng

doi:10.1186/s12967-024-05455-6

Intricate effects of post-translational modifications in liver cancer: mechanisms to clinical applications

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Published: 13 July 2024

Volume 22, article number 651, (2024)
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Intricate effects of post-translational modifications in liver cancer: mechanisms to clinical applications

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Yu Zhang¹^na1,
Weihao Xu¹^na1,
Chuanhui Peng¹,
Shenli Ren¹ &
…
Cheng Zhang¹

Abstract

Liver cancer is a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form, characterized by high incidence and mortality rates. Despite advances in targeted therapies and immunotherapies, the prognosis for advanced liver cancer remains poor. This underscores the urgent need for a deeper understanding of the molecular mechanisms underlying HCC to enable early detection and the development of novel therapeutic strategies. Post-translational modifications (PTMs) are crucial regulatory mechanisms in cellular biology, affecting protein functionality, interactions, and localization. These modifications, including phosphorylation, acetylation, methylation, ubiquitination, and glycosylation, occur after protein synthesis and play vital roles in various cellular processes. Recent advances in proteomics and molecular biology have highlighted the complex networks of PTMs, emphasizing their critical role in maintaining cellular homeostasis and disease pathogenesis. Dysregulation of PTMs has been associated with several malignant cellular processes in HCC, such as altered cell proliferation, migration, immune evasion, and metabolic reprogramming, contributing to tumor growth and metastasis. This review aims to provide a comprehensive understanding of the pathological mechanisms and clinical implications of various PTMs in liver cancer. By exploring the multifaceted interactions of PTMs and their impact on liver cancer progression, we highlight the potential of PTMs as biomarkers and therapeutic targets. The significance of this review lies in its potential to inform the development of novel therapeutic approaches and improve prognostic tools for early intervention in the fight against liver cancer.

Introduction

Liver cancer is the sixth most prevalent cancer (4.3% of all cancer sites) and the third leading cause of cancer-related mortality (7.8% of all cancer sites) worldwide, according to Global Cancer Statistics 2022 [1,2,3]. Hepatocellular carcinoma (HCC) accounts for 75–85% of liver cancer cases. The incidence of liver cancer shows notable geographical variations, with East Asia and Sub-Saharan Africa experiencing the highest rates, largely due to the varying prevalence of risk factors such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, aflatoxin exposure, chronic alcohol use, and non-alcoholic fatty liver disease (NAFLD) [4,5,6,7]. Recent strides in molecular biology have shed light on the complex interplay of genetic, epigenetic, and environmental factors in liver cancer pathogenesis [8,9,10,Full size image

Table 1 Effects and regulatory mechanisms of post-translational modifications in the carcinogenesis of liver cancer

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This review aims to highlight the critical role of PTMs in the pathogenesis and progression of liver cancer, emphasizing the most extensively explored PTMs, mainly including phosphorylation, acetylation, methylation, and glycosylation. By dissecting the intricate mechanisms through which PTMs influence key cellular processes in liver cancer, the paper seeks to elucidate their potential as therapeutic targets, discuss the challenges in targeting these modifications, and explore promising research directions (Table 2). Ultimately, this review aims to improve diagnostic accuracy, prognostic prediction, and the personalization of treatment strategies for liver cancer by leveraging the insights gained from the study of PTMs in HCC pathogenesis.

Table 2 Clinical significance of post-translational modifications in liver cancer

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Literature search strategy

To identify relevant and high-quality literature, we performed an extensive search across databases including PubMed, Scopus, and Web of Science. Our search was confined to articles published from January 2017 to April 2024. We used keywords such as “liver cancer,” “hepatocellular carcinoma,” “post-translational modifications,” “phosphorylation,” “acetylation,” “methylation,” “ubiquitination,” and “glycosylation.” We selected articles based on their pertinence to PTMs in HCC, emphasizing those that offer insights into molecular mechanisms, diagnostic implications, and therapeutic potential. After conducting the keyword searches, we focused on reviewing high-impact and high-quality articles. We prioritized studies that were most relevant to our research, ensuring a comprehensive coverage of the role of PTMs in liver cancer. This thorough screening process allowed us to incorporate the most pertinent findings and provide a detailed understanding of the role of PTMs in liver cancer.

Expression and role of PTMs in liver cancer

Phosphorylation and its implications in liver cancer

Increasing research has revealed a significant correlation between PTMs and the clinicopathological features and prognosis of patients with liver cancer [61,62,63,64]. Phosphorylation, as a pivotal PTM, is reported to have a strong association with tumor pathological grading and poor prognosis in liver cancer [65,66,67,

Availability of data and materials

Not applicable.

Abbreviations

HCC:: Hepatocellular carcinoma
PTMs:: Post-translational modifications
HBV:: Hepatitis B virus
HCV:: Hepatitis C virus
NAFLD:: Non-alcoholic fatty liver disease
CKB:: Creatine kinase B
TCGA:: The Cancer Genome Atlas
IHC:: Immunohistochemistry
IGF1R:: Insulin-like growth factor 1 receptor
GPX4:: Glutathione peroxidase 4
LOXL3:: Lysyl oxidase-like 3
EGF:: Epidermal growth factor
DHODH:: Dihydroorotate dehydrogenase
anti-PD1:: Anti-programmed cell death 1
ZFP64:: Zinc finger protein 64
PKCα:: Protein Kinase C alpha
CSF1:: Colony stimulating factor 1
TME:: Tumor microenvironment
PCK1:: Phosphoenolpyruvate carboxykinase 1
HSPA8:: Heat shock protein A8

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Funding

This study was supported by Natural Science Foundation exploration project of Zhejiang Province (LY21H030010), National Natural Science Foundation of China (82170673), and the Natural Science Foundation of Zhejiang Province (LQ20H030006).

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Yu Zhang and Weihao Xu have contributed equally to this work.

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Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Yu Zhang, Weihao Xu, Chuanhui Peng, Shenli Ren & Cheng Zhang

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Yu Zhang
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Weihao Xu
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Chuanhui Peng
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Shenli Ren
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Cheng Zhang
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All the authors contributed to the manuscript and reviewed and approved it as presented here. Yu Zhang and Weihao Xu contributed to the concept of the review and writing the manuscript. Chuanhui Peng and Shenli Ren, designed the figure. Cheng Zhang aided in revising the manuscript. All authors read and approved the final manuscript.

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Zhang, Y., Xu, W., Peng, C. et al. Intricate effects of post-translational modifications in liver cancer: mechanisms to clinical applications. J Transl Med 22, 651 (2024). https://doi.org/10.1186/s12967-024-05455-6

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Received: 14 April 2024
Accepted: 29 June 2024
Published: 13 July 2024
DOI: https://doi.org/10.1186/s12967-024-05455-6

Intricate effects of post-translational modifications in liver cancer: mechanisms to clinical applications

Abstract

Introduction

Literature search strategy

Expression and role of PTMs in liver cancer

Phosphorylation and its implications in liver cancer

Availability of data and materials

Abbreviations

References

Acknowledgements

Funding

Author information

Authors and Affiliations

Contributions

Corresponding author

Ethics declarations

Ethics approval and consent to participate

Consent for publication

Competing interests

Additional information

Publisher's Note

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About this article

Cite this article

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Intricate effects of post-translational modifications in liver cancer: mechanisms to clinical applications

Abstract

Introduction

Literature search strategy

Expression and role of PTMs in liver cancer

Phosphorylation and its implications in liver cancer

Availability of data and materials

Abbreviations

References

Acknowledgements

Funding

Author information

Authors and Affiliations

Contributions

Corresponding author

Ethics declarations

Ethics approval and consent to participate

Consent for publication

Competing interests

Additional information

Publisher's Note

Rights and permissions

About this article

Cite this article

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Keywords

Search

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