{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:36:36Z","timestamp":1790015796078,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006749","name":"Burapha University","doi-asserted-by":"crossref","award":["2.76\/2569"],"award-info":[{"award-number":["2.76\/2569"]}],"id":[{"id":"10.13039\/501100006749","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dysregulated magnesium (Mg2+) homeostasis contributes to colorectal cancer (CRC), yet its context-dependent function within the tumor microenvironment remains unresolved. This study aimed to determine how sustained low and high extracellular Mg2+ environments affect CRC spheroid (SP) growth and Mg2+ homeostasis using HT-29 SPs. We analyzed Mg2+ flux, the expression of Mg2+ transporters (e.g., Transient Receptor Potential Melastatin (TRPM) 6), viability, apoptotic and autophagic markers, and phospho-\/oxidoproteomic alterations. Both Mg2+ extremes destabilized SP architecture, reduced viability, and induced apoptosis and autophagy, with SPs displaying heightened vulnerability relative to 2D cultures. Mg2+ stress impaired Mg2+ influx and eliminated adaptive transporter regulation in SPs. Loss of membrane TRPM6\/7 heterodimers, driven by altered phosphorylation (e.g., TRPM6 Serine 141, Serine 1252, Threonine 1851) and elevated oxidation (e.g., Methionine 1755), suppressed channel activity. High Mg2+ caused profound metabolic failure despite increased total Mg2+, reflecting functional Mg2+ deficiency. CRC spheroids are acutely susceptible to Mg2+ imbalance due to collapsed transporter homeostasis and post-translational inhibition of Mg2+ channels. These findings reveal a targetable metabolic vulnerability and support the therapeutic potential of localized Mg2+ modulation in CRC.<\/jats:p>","DOI":"10.3390\/ijms27020834","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:12:04Z","timestamp":1768403524000},"page":"834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg2+ Homeostasis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6010-1709","authenticated-orcid":false,"given":"Nattida","family":"Kampuang","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2673-0807","authenticated-orcid":false,"given":"Pongsakorn","family":"Lapchock","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3659-976X","authenticated-orcid":false,"given":"Tanida","family":"Treerattanakulporn","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0415-2674","authenticated-orcid":false,"given":"Phossawee","family":"Kongkaew","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-6373","authenticated-orcid":false,"given":"Siriporn","family":"Chamniansawat","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2475-9161","authenticated-orcid":false,"given":"Narongrit","family":"Thongon","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Auwercx, J., Rybarczyk, P., Kischel, P., Dhennin-Duthille, I., Chatelain, D., Sevestre, H., Van Seuningen, I., Ouadid-Ahidouch, H., Jonckheere, N., and Gautier, M. 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