The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

Abstract

Pancreatic cancer is an aggressive cancer with low survival rates. Genetic and epigenetic dysregulation has been associated with the initiation and progression of pancreatic tumors. Multiple studies have pointed to the involvement of aberrant chromatin modifications in driving tumor behavior. ATP-dependent chromatin remodeling complexes regulate chromatin structure and have critical roles in stem cell maintenance, development, and cancer. Frequent mutations and chromosomal aberrations in the genes associated with subunits of the ATP-dependent chromatin remodeling complexes have been detected in different cancer types. In this review, we summarize the current literature on the genomic alterations and mechanistic studies of the ATP-dependent chromatin remodeling complexes in pancreatic cancer. Our review is focused on the four main subfamilies: SWItch/sucrose non-fermentable (SWI/SNF), imitation SWI (ISWI), chromodomain-helicase DNA-binding protein (CHD), and INOsitol-requiring mutant 80 (INO80). Finally, we discuss potential novel treatment options that use small molecules to target these complexes.

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

“…Epigenetic regulation has been extensively reviewed in association with various human biological processes, such as embryogenesis, cell differentiation, X chromosome inactivation, and pathologies such as cancer [ 40 , 41 ]. The best-characterized epigenetic mechanisms are DNA methylation and histone modifications; however, the epigenetic scenario is much more complicated with new players and new mechanisms including non-coding RNA (ncRNA)-mediated regulation, histone variants, and ATP-dependent chromatin remodeling [ 42 , 43 , 44 ]. All these discrete but reversible modifications may orchestrate extensive changes in chromatin structure and conformation, interfering with the transcriptional machinery’s ability to access its target genes and promoters [ 45 , 46 ].…”

Crosstalk between KRAS, SRC and YAP Signaling in Pancreatic Cancer: Interactions Leading to Aggressive Disease and Drug Resistance

“…Reciprocally, the absence of deubiquitinating enzyme BAP1 reduces the level of LATS1/2 leading to YAP activation and increased PDAC development in KC mice [152]. Accordingly, the expression of either ACTL6A or SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 2), a catalytic subunit of SWI/SNF [153], is associated with unfavorable prognosis while expression of BAP1 is correlated with favorable prognosis in PDAC patients.…”

BAF Complex in Embryonic Stem Cells and Early Embryonic Development

“…The ATP-dependent protein complexes with ATPase activity, termed chromatin remodeling complex, use the energy generated by hydrolysis of ATP to make the four changes in the nucleosomes structure and thereby regulate gene expression ( Figure 1 ) [ 15 ].…”