{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:05:19Z","timestamp":1789967119126,"version":"4.0.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colorectal cancer (CRC) remains a major cause of cancer death worldwide, largely due to metastasis and drug resistance. The epithelial\u2013mesenchymal transition (EMT) is known to drive CRC metastasis. ATM kinase has been reported to influence the Akt signaling pathway, which itself plays a central role in EMT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined whether the ATM inhibitor KU55933 could interfere with TGF-\u03b21-induced EMT in two human CRC cell lines, SW620 and HT29. Cells were exposed to TGF-\u03b21 with or without KU55933 (or KU60019). EMT was assessed by cell morphology and Western blotting for epithelial and mesenchymal markers. Migration was measured by wound healing assay, and invasion by Matrigel assay. Apoptosis and proliferation were evaluated by flow cytometry and MTT assay. To explore the underlying mechanism, we analyzed Akt pathway signaling by Western blot and performed KEGG pathway enrichment on gene expression changes. A xenograft model was also used to test the\n                      <jats:italic>in vivo<\/jats:italic>\n                      effect of KU55933 on tumor growth and EMT marker expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      KU55933 effectively reversed the morphological changes triggered by TGF-\u03b21. It reduced mesenchymal markers Vimentin and N-cadherin while upregulating the epithelial marker E-cadherin. At the mechanistic level, KU55933 was associated with reduced phospho-AKT Ser473 and phospho-GSK-3\u03b2 Ser9 signals, together with lower expression of the transcription factors ZEB1, Snail, and Twist-1. KEGG pathway analysis showed that differentially expressed genes between the TGF-\u03b21 and TGF-\u03b21 plus KU55933 groups were significantly enriched in the PI3K-Akt signaling pathway. Functionally, the inhibitor significantly suppressed TGF-\u03b21-driven migration and invasion and promoted apoptosis.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , KU55933 markedly inhibited tumor growth in the xenograft model; tumor tissues showed elevated E-cadherin and reduced N-cadherin and Ki-67.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data indicate that KU55933 and KU60019 attenuate TGF-\u03b21-induced EMT-associated phenotypes, migration, and invasion in CRC cells, accompanied by reduced AKT-related signaling, while also promoting apoptosis and suppressing xenograft growth. These findings support further investigation of pharmacological ATM inhibition as a potential strategy for limiting CRC progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1879298","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:29:18Z","timestamp":1789964958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The ATM inhibitor KU55933 inhibits TGF-\u03b21-mediated epithelial to mesenchymal transition in colorectal cancer cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuhan","family":"Ding","sequence":"first","affiliation":[{"name":"Department of General Surgery, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, 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