{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T10:42:45Z","timestamp":1776940965850,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, driven by complex genetic and epigenetic factors. The Williams syndrome transcription factor (WSTF\/BAZ1B), an emerging oncogenic factor, has been implicated in chromatin remodeling and genome stability. However, the precise mechanisms in CRC progression, particularly the metabolic reprogramming processes, remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study integrated transcriptomic, metabolomic, genome-wide ChIP-seq and summary-data-based Mendelian randomization (SMR) analyses in CRC cells and patient cohorts to study the WSTF regulatory network. WSTF knockdown and overexpression cell lines were combined with RNA-seq, LC-MS metabolomics and ChIP-seq annotation to identify direct targets and affected pathways. Multi-omics SMR using CRC GWAS, eQTL and mQTL datasets, together with bulk and single-cell RNA-seq, immune infiltration, functional assays and molecular docking were applied to explore GLYCTK as a candidate downstream effector of WSTF and a putative CRC-associated marker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WSTF knockdown reprogrammed transcription and metabolism, activating glucose and stress-response pathways while suppressing ribosome biogenesis, genetic information processing and MYC-related programs. ChIP-seq suggested that WSTF mainly binds to promoter-proximal, GC-rich motifs and identified GLYCTK as a candidate downstream target whose expression is inversely associated with WSTF. SMR analysis suggested a methylation-dependent regulatory relationship in which GLYCTK expression is associated with CRC risk. The immune infiltration analyses suggested that GLYCTK is associated with an immune-cold tumor microenvironment, whereas functional assays indicated that GLYCTK promotes proliferation, migration and invasion in CRC cells. Drug screening identified phenylbiguanide and hydroxyfasudil as candidate compounds targeting GLYCTK-associated networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>WSTF may contribute to CRC progression through transcriptional and epigenetic-associated regulation of metabolic adaptation, while GLYCTK may represent a context-dependent downstream factor associated with CRC susceptibility and development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1819148","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:57:03Z","timestamp":1776938223000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["WSTF-associated regulation of GLYCTK and metabolic adaptation in colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Liming","family":"Zhou","sequence":"first","affiliation":[{"name":"College of Life Sciences, North China University of Science and Technology","place":["Tangshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, North China University of Science and Technology","place":["Tangshan, China"]},{"name":"The Cancer Institute, Hebei Key Laboratory of Molecular Oncology, Tangshan People\u2019s Hospital","place":["Tangshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Li","sequence":"additional","affiliation":[{"name":"The Cancer Institute, Hebei Key Laboratory of Molecular Oncology, Tangshan People\u2019s Hospital","place":["Tangshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shasha","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Life Sciences, North China University of Science and Technology","place":["Tangshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimin","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Life Sciences, North China University of Science and Technology","place":["Tangshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Sciences, North China University of Science and Technology","place":["Tangshan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, North China University of Science and Technology","place":["Tangshan, 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