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World J Gastroenterol. Jan 14, 2022; 28(2): 188-198
Published online Jan 14, 2022. doi: 10.3748/wjg.v28.i2.188
Multiple subcellular localizations and functions of protein kinase Cδ in liver cancer
Kohji Yamada, Kiyotsugu Yoshida
Kohji Yamada, Kiyotsugu Yoshida, Department of Biochemistry, The Jikei University School of Medicine, Tokyo 105-8461, Japan
Author contributions: All authors contributed equally to the conception and design of the study, literature review, analysis, drafting, critical revision and editing, and approval of the final version.
Supported by the Japan Society for the Promotion of Science, KAKENHI Grant, No. 19H03519, 16K18434, and 18K15253 to Yamada K, No. 17H03584, 18K19484, and 20H03519 to Yoshida K; AMED under Grant No. A326TS to Yamada K; The Jikei University Graduate Research Fund to Yamada K; and the Science Research Promotion Fund to Yoshida K.
Conflict-of-interest statement: Authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kiyotsugu Yoshida, MD, PhD, Professor, Department of Biochemistry, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. kyoshida@jikei.ac.jp
Received: March 26, 2021
Peer-review started: March 26, 2021
First decision: June 14, 2021
Revised: June 25, 2021
Accepted: December 31, 2021
Article in press: December 31, 2021
Published online: January 14, 2022
Processing time: 291 Days and 0.3 Hours
Abstract

Protein kinase Cδ (PKCδ) is a member of the PKC family, and its implications have been reported in various biological and cancerous processes, including cell proliferation, cell death, tumor suppression, and tumor progression. In liver cancer cells, accumulating reports show the bi-functional regulation of PKCδ in cell death and survival. PKCδ function is defined by various factors, such as phosphorylation, catalytic domain cleavage, and subcellular localization. PKCδ has multiple intracellular distribution patterns, ranging from the cytosol to the nucleus. We recently found a unique extracellular localization of PKCδ in liver cancer and its growth factor-like function in liver cancer cells. In this review, we first discuss the structural features of PKCδ and then focus on the functional diversity of PKCδ based on its subcellular localization, such as the nucleus, cell surface, and extracellular space. These findings improve our knowledge of PKCδ involvement in the progression of liver cancer.

Keywords: Protein kinase Cδ; Liver cancer; Subcellular localization; Tumor suppression; Tumor progression

Core Tip: Protein kinase Cδ (PKCδ) plays multifunctional roles in various cancers, including liver cancer. PKCδ has been shown to exert pleiotropic functions through various stimuli responsiveness, post-translational modifications, and subcellular localization. Recently, we found that PKCδ is secreted extracellularly and resides on the cell surface of liver cancer cells, which contributes to tumorigenesis. In this review, we focus on the localization of PKCδ to discuss its characteristic localization patterns and functions in liver cancer, and outline the involvement of PKCδ localized intra- and extracellularly with distinct functions in the progression of liver cancer.