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Review
. 2023 Mar;62(3):36.
doi: 10.3892/ijo.2023.5484. Epub 2023 Feb 3.

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

Jian Wang  1 , Bo Yang  2 , Xiuhang Zhang  3 , Shuhan Liu  1 , Xiaoqiang Pan  1 , Changkai Ma  1 , Shiqiang Ma  1 , Dehai Yu  4 , Wei Wu  1
Affiliations
Review

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

Jian Wang et al. Int J Oncol. 2023 Mar.

Abstract

Chromobox (CBX) proteins are important epigenetic regulatory proteins and are widely involved in biological processes, such as embryonic development, the maintenance of stem cell characteristics and the regulation of cell proliferation and apoptosis. Disorder and dysfunction of CBXs in cancer usually lead to the blockade or ectoptic activation of developmental pathways, promoting the occurrence, development and progression of cancer. In the present review, the characteristics and functions of CBXs were first introduced. Subsequently, the expression of CBXs in cancers and the relationship between CBXs and clinical characteristics (mainly cancer grade, stage, metastasis and relapse) and prognosis were discussed. Finally, it was described how CBXs regulate cell proliferation and self‑renewal, apoptosis and the acquisition of malignant phenotypes, such as invasion, migration and chemoresistance, through mechanisms involving epigenetic modification, nuclear translocation, noncoding RNA interactions, transcriptional regulation, posttranslational modifications, protein‑protein interactions, signal transduction and metabolic reprogramming. The study also focused on cancer therapies targeting CBXs. The present review provides new insight and a comprehensive basis for follow‑up research on CBXs and cancer.

Keywords: biomarker; cancer; cancer therapy; chromatin modification; chromobox.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Conserved regions of CBX proteins. CBX, chromobox; aa, amino acid; PcG, polycomb group; HP1, heterochromatin protein 1.
Figure 2
Figure 2
Transcriptional repression by (A) PRCs and (B) HP1. PRC, polycomb repression complex; HP1, heterochromatin protein 1; CBX, chromobox; PHC, polyhomeotic-like protein; RING, really interesting new gene protein; PCGF, polycomb group ring finger protein; EZH1/2, enhancer of zeste homolog protein 1/2; EED, embryonic ectoderm development protein; SUZ12, suppressor of zeste protein 12; RBAP46/48, retinoblastoma binding-associated protein 46/48; H3K27, histone H3 lysine K27; CHD, chromodomain; CSD, chromoshadow domain.
Figure 3
Figure 3
Schematic representation of various regulatory mechanisms of CBXs in cancer. CBX, chromobox; PPI, protein-protein interaction; Ub, ubiquitin; PTM, posttranslational modification; ncRNA, noncoding RNA; lncRNA, long noncoding RNA; miRNA, microRNA; circRNA, circular RNA; ORF, open reading frame; H3K27me3, histone H3 lysine K27 trimethylation.
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Grants and funding

The present study was supported by grants from the Science and Technology Department of Jilin Province (grant nos. 20200201123JC and 20220402066GH to DY).