Regulation of Keratin Chemical Modifications: Potential Molecular Mechanisms in Proliferative Diseases

TL;DR

This review explores how chemical changes to keratin proteins may contribute to diseases like cancer and fibrosis, and how targeting these changes could lead to new treatments.

Contribution

The paper provides a systematic review of keratin post-translational modifications and their roles in disease progression, highlighting potential therapeutic strategies.

Findings

Keratin undergoes phosphorylation, acetylation, and methylation, which influence fibrosis and cancer progression.

Keratin modifications regulate signaling pathways that affect epithelial cell function and disease development.

Targeting keratin or its modifications through siRNAs or small molecules shows therapeutic promise.

Abstract

Keratin, a core structural protein in epithelial cells, is essential for maintaining epithelial tissue integrity. Numerous studies have confirmed its critical role in proliferative disorders, including lung/liver cancer, idiopathic pulmonary fibrosis (IPF), and hepatic fibrosis (HF). Post-translational modification (PTM) regulates protein activity, and keratin undergoes phosphorylation, acetylation, and methylation—modifications that modulate fibrosis and cancer progression by regulating relevant signaling pathways. However, how these modifications reshape keratin’s structure and function in these diseases remains understudied, underscoring the necessity for a systematic review. This review first summarizes keratin’s classification, physiological functions, and roles in epithelial cells, then focuses on the physiological significance of keratin modifications in fibrosis and cancer, while dissecting the molecular mechanisms by which keratin PTMs drive disease progression to address the knowledge gap regarding modification-related keratin changes. Elucidating the mechanisms of keratin and its PTMs is pivotal for understanding disease progression and developing targeted therapies; meanwhile, keratin-targeted strategies—such as keratin siRNAs and small-molecule compounds that regulate keratin expression or modification—have shown therapeutic potential. In summary, this review synthesizes current research findings and provides novel insights for the treatment of fibrosis and cancer.

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