YEATS2, encoding a scaffolding subunit of the ATAC complex, is an evolutionarily conserved reader of histone acylation marks (H3K27ac, H3K27cr, H3K27bz). It plays a pivotal role in bridging acyl-CoA metabolism to chromatin remodeling, regulating gene transcription, and is involved in multiple key pathways such as NF-κB, PI3K/AKT [5]. It is of great biological importance in processes like cell proliferation, survival, and tumorigenesis [1,2,3,4,6,7,8]. Genetic models, including KO/CKO mouse models, are valuable for studying its functions.

Depletion of YEATS2 in pancreatic ductal adenocarcinoma (PDAC) cells reduced their growth, survival, and tumorigenesis as YEATS2 is crucial for maintaining TAK1 activation and NF-κB transcriptional activity [1]. In hepatocellular carcinoma (HCC), knockdown of YEATS2 led to DNA damage, up-regulation of γ-H2A.X, activation of the p53/p21Cip1 pathway, and enhanced cell senescence, inhibiting tumor growth in nude mouse models [2]. In pancreatic cancer, YEATS2 inhibition decreased cell proliferation and migration in vitro and in vivo, and it was identified as a target of HIF1α [3]. In HCC, overexpression of YEATS2 promoted tumor cell proliferation, migration, and invasion through the PI3K/AKT signaling pathway [4]. In esophageal squamous cell carcinoma (ESCC), YEATS2 enhanced cell proliferation and migration by activating NF-κB signaling through H3K27ac-activated IL6ST [6]. In non-small cell lung cancer (NSCLC), depletion of YEATS2 reduced ATAC-complex-dependent promoter H3K9ac levels and deactivated essential gene expression [7].

In conclusion, YEATS2 is a key regulator in chromatin-related processes and is involved in the development of multiple cancers including PDAC, HCC, NSCLC, and ESCC. Model-based research, especially KO/CKO mouse models, has revealed its crucial roles in tumor cell survival, proliferation, migration, and immune-evasion-related pathways, providing potential therapeutic targets for these diseases.