Diversity roles of CHD1L in normal cell function and tumorigenesis

Abstract

Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is a multifunctional protein participated in diverse cellular processes, including chromosome remodeling, cell differentiation and development. CHD1L is a regulator of chromosomal integrity maintenance, DNA repair and transcriptional regulation through its bindings to DNA. By regulating kinds of complex networks, CHD1L has been identified as a potent anti-apoptotic and pro-proliferative factor. CHD1L is also an oncoprotein since its overexpression leads to dysregulation of related downstream targets in various cancers. The latest advances in the functional molecular basis of CHD1L in normal cells will be described in this review. As the same time, we will describe the current understanding of CHD1L in terms of structure, characteristics, function and the molecular mechanisms underlying CHD1L in tumorigenesis. We inference that the role of CHD1L which involve in multiple cellular processes and oncogenesis is well worth further studying in basic biology and clinical relevance.

Design, Synthesis, and Biological Evaluation of the First Inhibitors of Oncogenic CHD1L

“…CHD1L is unique from other chromatin remodelers and has a diverse repertoire of cellular functions . CHD1L is essential for poly ADP-ribose (PAR) polymerase (PARP)-mediated DNA repair and knockdown of CHD1L sensitizes tumor cells to DNA-damaging agents .…”

“…11 CHD1L is unique from other chromatin remodelers and has a diverse repertoire of cellular functions. 12 CHD1L is essential for poly ADP-ribose (PAR) polymerase (PARP)-mediated DNA repair and knockdown of CHD1L sensitizes tumor cells to DNA-damaging agents. 1 Two recent reports validate CHD1L as a significant factor promoting drug resistance to PARP inhibitors via CHD1L-mediated nucleosome sliding, alleviating PARP trapping by PARP inhibitors.…”

“…These results highlight the antitumor potential of CHD1Li. Furthermore, CHD1L has numerous biological functions 12 that could be exploited in combination with drugs that target other antitumor mechanisms, underlining CHD1L as an attractive anticancer drug target.…”

A pan-cancer analysis reveals CHD1L as a prognostic and immunological biomarker in several human cancers

“…CHD1L is an essential cellular protein that was found to be involved in many cellular processes such as chromosome remodeling and integrity maintenance, DNA repair, and controlling the transcriptional status of several genes through the binding with DNA ( Xiong et al, 2021 ). Additionally, many reports have correlated this gene with cell metastasis and tumorigenesis ( Liu Z. H. et al, 2017 ).…”

The validation of new CHD1L inhibitors as a therapeutic strategy for cancer

“…CHD1L is influenced by key cancer-driving pathways, including Wnt/β-catenin, PI3K/AKT, and Ras/MAPK [ 22 ]. Its diverse roles encompass regulating malignant gene expression, cell plasticity and stemness via epithelial-mesenchymal transition (EMT), cell survival, and metastatic potential [ 23 ]. Given the critical role of CHD1L in tumor progression, metastasis, and drug resistance, the identification of CHD1L inhibitors (CHD1Li) could lead to effective targeted therapies for CRC and other cancers.…”