{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:24:05Z","timestamp":1768508645469,"version":"3.49.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"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. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The phosphatase and tensin homolog (\n                      <jats:italic>PTEN<\/jats:italic>\n                      ) is a classical tumor-suppressor gene. Its expression deficiency concurrently drives disease progression in approximately 30% of melanomas and is closely associated with radiotherapy tolerance. However, there is a lack of systematic evidence regarding whether and how PTEN regulates the radiosensitivity of melanoma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The expression of PTEN was validated using TCGA database, clinical tissue microarrays, and multiple melanoma cell lines. PTEN knockdown (PTEN-KD) and PTEN overexpression (PTEN-OE) stable cell lines were constructed using lentiviral vectors. CCK-8, colony formation assay, annexin V\/PI flow cytometry, neutral comet assay, cell-cycle analysis, and Western blotting were used to assess the biological changes in cells after 0 Gy\u20138\u00a0Gy \u03b3-ray irradiation (IR). A cell-derived xenograft model was established, and the tumor volume was observed after local 10\u00a0Gy IR for 28 days; in addition, H&amp;amp;E, Ki67, and TUNEL evaluations were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression of PTEN in melanoma tissues and cell lines was significantly lower than that in normal controls. IR could induce a transient upregulation of PTEN followed by rapid downregulation. PTEN-OE significantly inhibited proliferation, reduced the clone survival rate, increased apoptosis, and weakened radiation-induced G\n                      <jats:sub>2<\/jats:sub>\n                      \/M phase arrest; however, the opposite was true for PTEN-KD. Mechanistically, PTEN-OE inhibited the DNA-PKcs axis, reduced NHEJ-mediated rapid repair, and increased the persistent expression of \u03b3-H2AX. PTEN-KD activated the p-ATM\/p-Chk2 signaling. Animal experiments confirmed that the tumor volume in the PTEN-OE + IR group was significantly lower than that in the NC + IR group, with an expanded necrotic area, a decreased Ki67 index, and an increased TUNEL-positive rate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PTEN enhances the radiosensitivity of melanoma by inhibiting the DNA-PKcs signal, weakening NHEJ repair, and delaying cell-cycle recovery. PTEN can serve as a biomarker for radiotherapy response prediction and a target for sensitization intervention, providing an experimental basis for precise radiotherapy strategies for melanoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2025.1712429","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:15:28Z","timestamp":1768454128000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PTEN enhances the radiosensitivity of melanoma by inhibiting DNA-PKcs"],"prefix":"10.3389","volume":"13","author":[{"given":"Shengqian","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Changhai Hospital, Second Military Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Changhai Hospital, Second Military Medical University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangjian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, The First Affiliated Hospital of Ningbo University","place":["Ningbo, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1007\/s00018-011-0878-0","article-title":"Genetic alterations of PTEN in human melanoma","volume":"69","author":"Aguissa-Tour\u00e9","year":"2012","journal-title":"Cell Mol. 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