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World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1425-1439
Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1425
Proliferating cell nuclear antigen clamp associated factor, a potential proto-oncogene with increased expression in malignant gastrointestinal tumors
Li-Juan Liu, Jian-Ming Liao, Fan Zhu
Li-Juan Liu, Jian-Ming Liao, Fan Zhu, State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy & Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei Province, China
Jian-Ming Liao, Department of Neurosurgery, Renmin Hospital, Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Liu LJ, Liao JM, and Zhu F co-wrote the paper; Liu LJ and Zhu F revised the paper; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81971943 and No. 81772196; and the Hubei Provincial Natural Science Foundation of China, No. 2020CFB656.
Conflict-of-interest statement: The 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fan Zhu, PhD, Professor, State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy & Immunology, Department of Medical Microbiology, School of Medicine, Wuhan University, No. 185 Donghu Rd, Wuhan 430071, Hubei Province, China. fanzhu@whu.edu.cn
Received: February 22, 2021
Peer-review started: February 22, 2021
First decision: June 4, 2021
Revised: June 11, 2021
Accepted: July 23, 2021
Article in press: July 23, 2021
Published online: October 15, 2021
Processing time: 233 Days and 1.1 Hours
Abstract

Gastrointestinal (GI) cancers, including malignancies in the gastrointestinal tract and accessory organs of digestion, represent the leading cause of death worldwide due to the poor prognosis of most GI cancers. An investigation into the potential molecular targets of prediction, diagnosis, prognosis, and therapy in GI cancers is urgently required. Proliferating cell nuclear antigen (PCNA) clamp associated factor (PCLAF), which plays an essential role in cell proliferation, apoptosis, and cell cycle regulation by binding to PCNA, is a potential molecular target of GI cancers as it contributes to a series of malignant properties, including tumorigenesis, epithelial-mesenchymal transition, migration, and invasion. Furthermore, PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer. In addition to GI cancers, PCLAF is also involved in other types of cancers and autoimmune diseases. Several pivotal pathways, including the Rb/E2F pathway, NF-κB pathway, and p53-p21 cascade, are implicated in PCLAF-mediated diseases. PCLAF also contributes to some diseases through dysregulation of the p53 pathway, WNT signal pathway, MEK/ERK pathway, and PI3K/AKT/mTOR signal cascade. This review mainly describes in detail the role of PCLAF in physiological status and GI cancers. The signaling pathways involved in PCLAF are also summarized. Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.

Keywords: Proliferating cell nuclear antigen; Proliferating cell nuclear antigen clamp associated factor; Transcript variant; Gastrointestinal cancers; Signal pathway; Biological therapeutic

Core Tip: In the interaction with proliferating cell nuclear antigen (PCNA), PCNA clamp associated factor (PCLAF) plays a crucial role in cell proliferation, DNA repair, and cell cycle regulation. PCLAF shows a causal relationship with gastrointestinal (GI) cancers as PCLAF is highly expressed in GI tumors and predicts poor prognosis. PCLAF is also associated with numerous other malignancies and autoimmune diseases. This review discusses the role of PCLAF in GI cancers, as well as the underlying molecular mechanism. Biological therapeutics by targeting PCLAF in cancers are also discussed.