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This study identifies Calcium\/calmodulin\u2010dependent protein kinase I (CAMK1) as a crucial regulator of anoikis in CRC progression. We analyzed\n                    <jats:italic>CAMK1<\/jats:italic>\n                    expression in CRC tissues and its correlation with patient prognosis. In\u00a0vitro,\n                    <jats:italic>CAMK1<\/jats:italic>\n                    was overexpressed in CRC cell lines to assess its effects on proliferation, migration, invasion, and anoikis resistance. In\u00a0vivo, mouse models were established to evaluate the impact of\n                    <jats:italic>CAMK1<\/jats:italic>\n                    overexpression on tumor growth and liver metastasis. Mechanistically, we examined the interaction between CAMK1 and Phosphoinositide 3\u2010kinase (PI3K), as well as the phosphorylation of PI3K and the activation of the downstream Protein kinase B (AKT) pathway. Mitochondrial function indicators were simultaneously measured: membrane potential, reactive oxygen species (ROS) production, and apoptosis markers, including the Bax\/Bcl\u20102 ratio and Caspase\u20103 activation. Rescue experiments were conducted using the PI3K activator 740 Y\u2010P.\n                    <jats:italic>CAMK1<\/jats:italic>\n                    expression was significantly downregulated in CRC tissues, and low\n                    <jats:italic>CAMK1<\/jats:italic>\n                    levels correlated with poor patient prognosis. In\u00a0vitro, overexpression of\n                    <jats:italic>CAMK1<\/jats:italic>\n                    significantly inhibited the malignant phenotypes of CRC cells and sensitized them to anoikis. Consistently,\n                    <jats:italic>CAMK1<\/jats:italic>\n                    overexpression suppressed tumor growth and hepatic metastasis in mouse models. Mechanistically, CAMK1 interacted with PI3K, inhibiting its phosphorylation and subsequent AKT pathway activation. This inhibition induced mitochondrial dysfunction, characterized by depolarization of the mitochondrial membrane potential and increased ROS production, and promoted apoptosis, as evidenced by an elevated Bax\/Bcl\u20102 ratio and Caspase\u20103 activation. Notably, the PI3K activator 740 Y\u2010P effectively reversed the pro\u2010anoikis effects and mitochondrial alterations induced by\n                    <jats:italic>CAMK1<\/jats:italic>\n                    , confirming the pivotal role of the PI3K\/AKT pathway in this regulation.\n                    <jats:italic>CAMK1<\/jats:italic>\n                    functions as a novel tumor suppressor in CRC. It constrains anoikis resistance and metastasis by inhibiting the PI3K\/AKT signaling pathway, thereby disrupting mitochondrial function. These findings highlight the dual potential of\n                    <jats:italic>CAMK1<\/jats:italic>\n                    as both a prognostic biomarker and therapeutic target in colorectal cancer.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600481rr","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:06:38Z","timestamp":1779512798000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CAMK1<\/scp>\n                    Suppresses Anoikis Resistance and Liver Metastasis in Colorectal Cancer"],"prefix":"10.1096","volume":"40","author":[{"given":"Qiang","family":"Feng","sequence":"first","affiliation":[{"name":"Laboratory Animal Center, College of Animal Science Jilin University  Changchun China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery, General Surgery Centre First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Hao","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Changchun University of Chinese Medicine  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjun","family":"Jin","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, College of Animal Science Jilin University  Changchun 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Hepatobiliary and Pancreatic Surgery, General Surgery Centre First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0464-1596","authenticated-orcid":false,"given":"Dongxu","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, College of Animal Science Jilin University  Changchun 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