{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:16Z","timestamp":1787030716687,"version":"build-2736575974"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460298"],"award-info":[{"award-number":["82460298"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To elucidate the role and molecular mechanism of the ER\u03b136\u2013SLC7A5\/LAT1 signaling axis in the malignant progression of cervical cancer and its sensitivity to boron neutron capture therapy (BNCT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic data from TCGA (n=296) and GTEx (n=10) were integrated to analyze SLC7A5 expression and its clinicopathological associations. Multiplex immunofluorescence staining was performed on a tissue microarray containing 99 cervical cancer specimens for spatial phenotyping. SiHa cell lines with stable ER\u03b136 knockdown or overexpression were established using lentiviral transduction. CCK-8, flow cytometry, wound healing, Transwell, and colony formation assays were used to assess the effects of ER\u03b136 on malignant phenotypes. Co-immunoprecipitation, Western blot, and qRT-PCR were employed to explore the interaction between ER\u03b136 and LAT1 as well as downstream signaling changes. The impact of ER\u03b136 on BNCT sensitivity was evaluated in both cellular and subcutaneous xenograft nude mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SLC7A5 was significantly upregulated in cervical cancer tissues and correlated with M stage and poor prognosis. ER\u03b136 and SLC7A5 exhibited robust spatial co-expression in the tumor microenvironment, and the double-positive phenotype was associated with shorter overall survival (P&amp;lt;0.05). ER\u03b136 interacted with LAT1 and was associated with elevated CD98hc and EGFR expression. Knockdown of ER\u03b136 suppressed proliferation, migration, and colony formation while promoting apoptosis; overexpression produced opposite effects. In BNCT simulation experiments, ER\u03b136 knockdown markedly attenuated BNCT-induced cytotoxicity, as evidenced by increased colony formation, reduced apoptosis, and altered S-phase distribution. Both cellular and animal models consistently showed downregulation of ER\u03b136 and LAT1 protein expression after BNCT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The ER\u03b136\u2013SLC7A5\/LAT1 axis associated with malignant phenotypes and BNCT sensitivity in cervical cancer. The ER\u03b136+\/SLC7A5+ spatial double-positive phenotype may represent a prognostic biomarker, and ER\u03b136 may serve as a predictive marker for BNCT response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1902977","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:52Z","timestamp":1787027332000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ER\u03b136 is associated with SLC7A5\/LAT1 expression, cervical cancer progression, and BNCT response: a translational study"],"prefix":"10.3389","volume":"16","author":[{"given":"Lili","family":"Zhang","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, The First Hospital of Lanzhou University","place":["Lanzhou, China"]},{"name":"School of Nuclear Science and Technology, Lanzhou University","place":["Lanzhou, 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