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Review
. 2022 May 20;12(9):4374-4385.
doi: 10.7150/thno.72966. eCollection 2022.

Recent advances in understanding the role of HES6 in cancers

Imène Krossa  1   2 , Thomas Strub  1   2 , Arnaud Martel  1   3 , Sacha Nahon-Esteve  1   3 , Sandra Lassalle  1   4 , Paul Hofman  1   4 , Stéphanie Baillif  1   3 , Robert Ballotti  1   2 , Corine Bertolotto  1   2
Affiliations
Review

Recent advances in understanding the role of HES6 in cancers

Imène Krossa et al. Theranostics. .

Abstract

The NOTCH signaling system regulates a variety of cellular processes during embryonic development and homeostasis maintenance in different tissues and contexts. Hence, dysregulation of NOTCH signaling is associated with a plethora of human cancers, and there have been multiple efforts to target key components of this pathway. In this review, we briefly highlight the latest research advances in understanding HES6, a poorly studied component of the NOTCH pathway. We summarize the role of HES6 in cancers with a focus on uveal melanoma. Finally, we discuss the ongoing efforts to target the NOTCH-HES6 axis in cancers.

Keywords: HES6; NOTCH; cancers; signaling; uveal melanoma.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Schematic representation of the canonical and noncanonical NOTCH signaling pathways. A. The canonical Notch signaling pathway is activated by ligand-receptor interactions leading to NICD release and translocation to the nucleus to form a transcriptional activation complex after binding to MAML-1 and CSL. Noncanonical NOTCH signaling regulates target gene expression via mechanisms that do not implicate HES factors. B. Structure of HES factors with conserved domains.
Figure 2
Figure 2
HES6 and DLL4 are associated with metastasis formation and a poor prognosis. The y-axis shows the log(2)-expression in patients who did not develop metastasis after a 2-year follow-up versus those who developed metastasis (Mets) before 18 months since UM diagnosis (Mets: No/Yes). Values indicated at the top of the figure correspond to log(2)-fold changes and p values of metastatic versus nonmetastatic patients. B. Kaplan-Meier curves showing overall survival stratified by HES6 and DLL4 expression (UM-TCGA dataset).
Figure 3
Figure 3
Expression of HES/HEY members and correlation with prognosis of the NOTCH family. Relative expression of HES/HEY gene family (UM-TCGA dataset).
Figure 4
Figure 4
Scheme of upstream regulators and downstream effectors of HES6 described in different cancers. The nodes identified in uveal melanomas are shown in red.
Figure 5
Figure 5
Expression of HDAC4 and CHAC1 and their correlation with prognosis. A. Kaplan-Meier curves showing overall survival stratified by HDAC4 and CHAC1 expression (UM-TCGA dataset). B. Expression correlation between HES6 and HDAC4 or CHAC1 (https://www.cbioportal.org).
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