{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:52:47Z","timestamp":1791377567510,"version":"4.3.2"},"reference-count":75,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["EMR\/2016\/007034"],"award-info":[{"award-number":["EMR\/2016\/007034"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["IIRP\u20102023\u20102134"],"award-info":[{"award-number":["IIRP\u20102023\u20102134"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The regulation of gene expression and its connection to the dynamics of plasma membrane signaling hubs (lipid rafts) have largely remained unexplored to date. Ras signaling plays crucial roles in the initiation and progression of colon adenocarcinoma (COAD) by regulation of gene expression, including DNA methyltransferase 1 (DNMT1). Gene\u2010specific hypermethylation and genome\u2010wide hypomethylation are well characterized in various cancers, including COAD. In view of this, we have examined how the signaling pathway orchestrated by plasma membrane\u2010associated lipid rafts coordinates with the epigenetic modifications that precisely modulate a specific group of (hub) genes involved. First, we have identified COAD\u2010specific hub genes (\n                    <jats:italic>COL1A1, COL1A2, COL4A1, SPP1, SPARC<\/jats:italic>\n                    , and\n                    <jats:italic>THBS2<\/jats:italic>\n                    ) through extensive bioinformatics analyses, which revealed that increased expression of these hub genes facilitates the onset and progression of COAD. Comprehensive computational analyses of methylation patterns confirmed that atypical hypomethylation at these gene loci elevates their expression in COAD. Thereafter, we have explored how the dynamics of plasma membrane signaling hubs\u2032, such as lipid rafts, influence gene\u2010specific promoter methylation dynamics within the nucleus of COAD cells. Our experimental analyses indicated that the transient destabilization (TD) of lipid rafts through ectopic cholesterol efflux activates the epidermal growth factor (EGF)\u2010independent lipid raft\u2010associated epidermal growth factor receptor (EGFR)\u2010rat sarcoma (RAS)\u2010mitogen\u2010activated protein kinase (MAPK) signaling pathway, leading to increased expression of DNMTs and decreased expression of hub genes in COAD cells. These results strongly suggest that the plasma membrane lipid raft\u2010associated EGFR\u2010RAS\u2010MAPK axis, functioning from membrane signaling hubs, can regulate genes located in various chromosomal locations. Ectopic expressions of DNMT1 impose an epigenetic checkpoint at those target loci by methylation of promoter DNA of the respective genes. We conclude that, gene specific hypomethylation of some genes, including\n                    <jats:italic>COL1A1, COL1A2, COL4A1, SPP1, SPARC<\/jats:italic>\n                    , and\n                    <jats:italic>THBS2<\/jats:italic>\n                    drives COAD and would serve as potential markers for COAD screening.\n                  <\/jats:p>","DOI":"10.1002\/mc.70085","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:01:00Z","timestamp":1770314460000},"page":"465-492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Comprehensive Gene Expression Analysis of Extensive Cohorts From Colon Adenocarcinoma Uncovered a Set of Genes Regulated by DNA Hypomethylation and Predominantly Influenced by Lipid Raft\u2010Mediated EGFR\u2010RAS\u2010MAPK Signaling"],"prefix":"10.1002","volume":"65","author":[{"given":"Ankan","family":"Roy","sequence":"first","affiliation":[{"name":"Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science National Institute of Technology Rourkela Odisha India"},{"name":"Department of Life Science ICMR\u2010Collaborative Centre of Excellence, National Institute of Technology Rourkela Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Niharika","sequence":"additional","affiliation":[{"name":"Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science National Institute of Technology Rourkela Odisha India"},{"name":"Department of Life Science ICMR\u2010Collaborative Centre of Excellence, National Institute of Technology Rourkela Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerbhan","family":"Kesarwani","sequence":"additional","affiliation":[{"name":"Biotechnology Division The Himalayan Centre for High\u2010throughput Computational Biology (HiCHiCoB, A BIC supported by DBT, India), CSIR\u2010Institute of Himalayan Bioresources Technology Palampur Himachal Pradesh India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4004-8047","authenticated-orcid":false,"given":"Ravi","family":"Shankar","sequence":"additional","affiliation":[{"name":"Biotechnology Division The Himalayan Centre for High\u2010throughput Computational Biology (HiCHiCoB, A BIC supported by DBT, India), CSIR\u2010Institute of Himalayan Bioresources Technology Palampur Himachal Pradesh India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir Kumar","family":"Patra","sequence":"additional","affiliation":[{"name":"Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science National Institute of Technology Rourkela Odisha India"},{"name":"Department of Life Science ICMR\u2010Collaborative Centre of Excellence, National Institute of Technology Rourkela Odisha 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