{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:12:33Z","timestamp":1790341953939,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T00:00:00Z","timestamp":1692057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["20H03616"],"award-info":[{"award-number":["20H03616"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Most solid tumors contain hypoxic and nutrient-deprived microenvironments. The cancer cells in these microenvironments have been reported to exhibit radioresistance. We have previously reported that nutrient starvation increases the expression and\/or activity of ATM and DNA-PKcs, which are involved in the repair of DNA double-strand breaks induced by ionizing radiation. In the present study, to elucidate the molecular mechanisms underlying these phenomena, we investigated the roles of AMPK and FOXO3a, which play key roles in the cellular response to nutrient starvation. Nutrient starvation increased clonogenic cell survival after irradiation and increased the activity and\/or expression of AMPK\u03b1, FOXO3a, ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2 in MDA-MB-231 cells. Knockdown of AMPK\u03b1 using siRNA suppressed the activity and\/or expression of FOXO3a, ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2 under nutrient starvation. Knockdown of FOXO3a using siRNA suppressed the activity and\/or expression of AMPK\u03b1, ATM, DNA-PKcs, FOXO3a, Src, EGFR, PDK1, and SOD2 under nutrient starvation. Nutrient starvation decreased the incidence of apoptosis after 8 Gy irradiation. Knockdown of FOXO3a increased the incidence of apoptosis after irradiation under nutrient starvation. AMPK and FOXO3a appear to be key molecules that induce radioresistance under nutrient starvation and may serve as targets for radiosensitization.<\/jats:p>","DOI":"10.3390\/ijms241612828","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:06:16Z","timestamp":1692097576000},"page":"12828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["AMPK\/FOXO3a Pathway Increases Activity and\/or Expression of ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2 and Induces Radioresistance under Nutrient Starvation"],"prefix":"10.3390","volume":"24","author":[{"given":"Yusuke","family":"Urushihara","sequence":"first","affiliation":[{"name":"Department of Radiation Biology, School of Medicine, Tohoku University, Sendai 980-8575, Japan"},{"name":"Kobe Research Lab, Oncolys BioPharma Inc., Kobe 650-0047, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8762-6027","authenticated-orcid":false,"given":"Takuma","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, School of Medicine, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Fujishima","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, School of Medicine, Tohoku University, Sendai 980-8575, Japan"},{"name":"Department of Risk Analysis and Biodosimetry, Institute of Radiation Emergency Medicine, Hirosaki University, Hirosaki 036-8562, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3434-594X","authenticated-orcid":false,"given":"Yoshio","family":"Hosoi","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, School of Medicine, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.3394","article-title":"Microenvironmental Regulation of Tumor Progression and Metastasis","volume":"19","author":"Quail","year":"2013","journal-title":"Nat. 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