Revealing the Roles of Keratin 8/18-Associated Signaling Proteins Involved in the Development of Hepatocellular Carcinoma.

Younglan Lim,Nam-On Ku

doi:10.3390/ijms22126401

Abstract

Although hepatocellular carcinoma (HCC) is developed with various etiologies, protection of hepatocytes seems basically essential to prevent the incidence of HCC. Keratin 8 and keratin 18 (K8/K18) are cytoskeletal intermediate filament proteins that are expressed in hepatocytes. They maintain the cell shape and protect cells under stress conditions. Their protective roles in liver damage have been described in studies of mouse models, and K8/K18 mutation frequency in liver patients. Interestingly, K8/K18 bind to signaling proteins such as transcription factors and protein kinases involved in HCC development. Since K8/K18 are abundant cytoskeletal proteins, K8/K18 binding with the signaling factors can alter the availability of the factors. Herein, we discuss the potential roles of K8/K18 in HCC development.

Highlights

Liver cancer was the third leading cause of cancer-related death in 2020, and about 90% of liver cancers are hepatocellular carcinoma (HCC) [1,2]
Virus (HCV) infection increases the risk of HCC incidence, and chronic liver diseases, such as cirrhosis and steatohepatitis, contribute to HCC development [5]
We summarize the general risk factors of HCC development and discuss the potential roles of

Summary

Introduction

Liver cancer was the third leading cause of cancer-related death in 2020, and about 90% of liver cancers are hepatocellular carcinoma (HCC) [1,2]. Habits such as alcohol abuse and smoking lead to the development of HCC by aggravating liver diseases and/or increasing genetic mutations [5]. Keratin 8 and keratin 18 are the major intermediate filament proteins expressed in hepatocytes [6] These keratins support cell structure and prevent mechanical stresses by spreading throughout the cytosol [8,9]. Since chronic liver damage elevates HCC incidence, K8/K18 defects might be one of the factors that can increase HCC incidence. Abundant cytoplasmic K8/K18 regulates signaling pathways by interacting with signaling factors and altering their availability and location [11,12] This K8/K18-mediated regulation can change cell cycle initiation and cell proliferation/migration, which subsequently causes HCC development. K8/K18 in altering the risk factors that contribute to HCC incidence

Liver Diseases

The Mutations and the Molecular Aspects of HCC Driver Genes

HCC Management

A Role of Signaling Protein

Findings

Conclusions