Histone Chaperones and Digestive Cancer: A Review of the Literature

Abstract

Background: The global burden of digestive cancer is expected to increase. Therefore, crucial for the prognosis of patients with these tumors is to identify early diagnostic markers or novel therapeutic targets. There is accumulating evidence connecting histone chaperones to the pathogenesis of digestive cancer. Histone chaperones are now broadly defined as a class of proteins that bind histones and regulate nucleosome assembly. Recent studies have demonstrated that multiple histone chaperones are aberrantly expressed and have distinct roles in digestive cancers. Objective: The purpose of this review is to present the current evidence regarding the role of histone chaperones in digestive cancer, particularly their mechanism in the development and progression of esophageal, gastric, liver, pancreatic, and colorectal cancers. In addition, the prognostic significance of particular histone chaperones in patients with digestive cancer is discussed. Methods: According to PRISMA guidelines, we searched the PubMed, Embase, and MEDLINE databases to identify studies on histone chaperones and digestive cancer from inception until June 2022. Results: A total of 104 studies involving 21 histone chaperones were retrieved. Conclusions: This review confirms the roles and mechanisms of selected histone chaperones in digestive cancer and suggests their significance as potential prognostic biomarkers and therapeutic targets. However, due to their non-specificity, more research on histone chaperones should be conducted in the future to elucidate novel strategies of histone chaperones for prognosis and treatment of digestive cancer.

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

“…Defining the FACT complex as a novel target for cancer treatment enabled researchers to investigate Curaxin as a therapeutic treatment for HCC patients [ 32 ]. Curaxin, a small molecular inhibitor of FACT that induces chromatin trapping of FACT and significantly inhibits normal human FACT activities, causes intracellular acidification and apoptosis of cancer cells [ 31 , 33 ].…”

“…(A) Potential implication of ASF1A in GM-CSFdependent inflammatory pathway.ASF1A inhibits the over-expression of GM-CSF. ASF1A depletion (dashed box) blocks (red cross) the inhibition pathway, which leads to the over-expression of GM-CSF, establishing an anti-tumor immunogenic response[32]. (B) The potential implication of ASF1A in Wnt signaling pathway is to cause the over-expression of β-catenin, which stimulates oncogene transcription[40].…”

Contribution of histone variants to aneuploidy: a cancer perspective

“…Histone chaperones are tightly linked to histone function, as their role in deposition and histone level control ensures an appropriate balance of incorporation and exchange (Hammond et al, 2017), which can be compromised during carcinogenesis. Like histone genes, histone chaperone genes are also dysregulated in cancer, including the H3-H4-cargoing chaperones ASF1, HIRA, CAF-1, DAXX, and DEK, the H3-H4 and H2A-H2B chaperone FACT, and the CENP-A-H4 chaperone HJURP (Ray- Gallet and Almouzni, 2022;Zhao et al, 2022). In terms of contribution to aneuploidy, several studies have shown the importance of histone chaperones in maintaining chromosomal stability, including increased levels of aneuploidy upon loss of FACT (Prendergast et al, 2020), ASF1 (Horard et al, 2018) and HJURP (Filipescu et al, 2017), mitotic defects and micronuclei following overexpression of DEK (Matrka et al, 2015), and expansion of ribosomal DNA (rDNA) repeats in absence of ASF1 (Houseley and Tollervey, 2011), which can be a source of chromosomal aberrations if inappropriately resolved (Daniloski et al, 2019).…”

Cancer Epigenetic Biomarkers

“…Histone chaperones are required for histone storage, transport, post-translational modifications, nucleosome assembly, and histone turnover. The third review in this Special Issue describes the role of selected histone chaperones in the progression of digestive cancers and their prognostic significance [9].…”