{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:01:50Z","timestamp":1792047710556,"version":"4.4.0"},"reference-count":46,"publisher":"American Association for Cancer Research (AACR)","issue":"3","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":105,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270767"],"award-info":[{"award-number":["32270767"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472884"],"award-info":[{"award-number":["82472884"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072695"],"award-info":[{"award-number":["82072695"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403209"],"award-info":[{"award-number":["82403209"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0805500"],"award-info":[{"award-number":["2021YFA0805500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DFCI Pussycat Foundation Helen Gurley Brown Presidential Initiative"},{"DOI":"10.13039\/501100013105","name":"Shanghai Rising-Star Program","doi-asserted-by":"publisher","award":["24YF2705700"],"award-info":[{"award-number":["24YF2705700"]}],"id":[{"id":"10.13039\/501100013105","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special Program for Clinical Research of Shanghai Municipal Commission of Health","award":["20244Y0074"],"award-info":[{"award-number":["20244Y0074"]}]},{"DOI":"10.13039\/100017633","name":"Shanghai Anticancer Association","doi-asserted-by":"crossref","award":["EYAS PROJECT SACA-CY23A05"],"award-info":[{"award-number":["EYAS PROJECT SACA-CY23A05"]}],"id":[{"id":"10.13039\/100017633","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA168504"],"award-info":[{"award-number":["CA168504"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA210057"],"award-info":[{"award-number":["CA210057"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA231945"],"award-info":[{"award-number":["CA231945"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Loss of the tumor-suppressor PTEN drives cancer progression and therapeutic resistance, yet no targeted therapies exist for PTEN-deficient tumors. In this study, we identify a critical druggable mechanism in which PTEN loss induces PI3K\u03b2 phosphorylation for tumorigenesis. Using the BioID interactome, we uncovered a phosphorylation-dependent PI3K\u03b2\u2013EPHA2 interaction in PTEN-null cells, driven by p-PI3K\u03b2Y962. PTEN functions as a tyrosine phosphatase that normally dephosphorylates p-PI3K\u03b2Y962. In PTEN-deficient contexts, enhanced p-PI3K\u03b2Y962 forms a complex with EPHA2 and SRC, in which both kinases contribute to PI3K\u03b2 phosphorylation, activating oncogenic pERK\/c-MYC and pAKT pathways. We developed a selective p-PI3K\u03b2Y962 antibody detecting p-PI3K\u03b2Y962 in PTEN-deficient tumors across preclinical models and clinical tumor specimens. Disrupting p-PI3K\u03b2Y962 suppressed tumor growth in multiple PTEN-null models. Dasatinib, an FDA-approved SRC\/EPHA2 inhibitor, effectively reduced p-PI3K\u03b2Y962 and inhibited tumor progression in PTEN-null but not PTEN wild-type tumors. These findings establish p-PI3K\u03b2Y962 as a druggable target and biomarker for developing targeted therapy in PTEN-deficient cancers beyond conventional PI3K kinase inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>We revealed a critical new mechanism that PTEN loss induces PI3K\u03b2 phosphorylation and EPHA2\/SRC\/p-PI3K\u03b2Y962 complex signaling to drive tumorigenesis. This work directs pharmaceutical development of p-PI3K\u03b2Y962 inhibitors and biomarker-driven clinical trials repurposing dasatinib for PTEN-deficient solid tumor treatment, with potential to significantly improve outcomes of broad patients with PTEN-deficient tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-25-1126","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T21:17:11Z","timestamp":1763155031000},"page":"521-540","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PTEN Loss Promotes PI3K\u03b2 Phosphorylation and EPHA2\/SRC\/p-PI3K\u03b2Y962 Complex Assembly to Drive Tumorigenesis"],"prefix":"10.1158","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3501-7836","authenticated-orcid":false,"given":"Shuang","family":"Tang","sequence":"first","affiliation":[{"name":"1Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China."},{"name":"2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China."},{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."},{"name":"5Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1471-6651","authenticated-orcid":false,"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"1Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China."},{"name":"2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4609-8448","authenticated-orcid":false,"given":"Johann S.","family":"Bergholz","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2665-4076","authenticated-orcid":false,"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3834-0951","authenticated-orcid":false,"given":"Weihua","family":"Wang","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6258-1777","authenticated-orcid":false,"given":"Renlei","family":"Ji","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3571-9288","authenticated-orcid":false,"given":"Wendi","family":"Huang","sequence":"additional","affiliation":[{"name":"6Bio-Med Big Data Center, Chinese Academy of Sciences Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6089-2733","authenticated-orcid":false,"given":"Jiachen","family":"Wu","sequence":"additional","affiliation":[{"name":"1Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China."},{"name":"2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China."},{"name":"7State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1468-4151","authenticated-orcid":false,"given":"Yutong","family":"Li","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3801-6409","authenticated-orcid":false,"given":"Xiaochun","family":"Wan","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8171-9505","authenticated-orcid":false,"given":"Xiadi","family":"He","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9003-4339","authenticated-orcid":false,"given":"Qianchen","family":"Jing","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7120-5535","authenticated-orcid":false,"given":"Menghong","family":"Sun","sequence":"additional","affiliation":[{"name":"8Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1802-6527","authenticated-orcid":false,"given":"Jared L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"9Department of Cell Biology, Harvard Medical School, Boston, Massachusetts."},{"name":"10Meyer Cancer Center, Weill Cornell Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6574-7314","authenticated-orcid":false,"given":"Tomer M.","family":"Yaron-Barir","sequence":"additional","affiliation":[{"name":"9Department of Cell Biology, Harvard Medical School, Boston, Massachusetts."},{"name":"11Englander Institute for Precision Medicine, Institute for Computational Biomedicine, Weill Cornell Medicine, New York, New York."},{"name":"12Columbia University Vagelos College of Physicians and Surgeons, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-2332","authenticated-orcid":false,"given":"Da-Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"1Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China."},{"name":"2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-3581","authenticated-orcid":false,"given":"Bo","family":"Dai","sequence":"additional","affiliation":[{"name":"13Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6605-3637","authenticated-orcid":false,"given":"Zefeng","family":"Wang","sequence":"additional","affiliation":[{"name":"14Department of Systems Biology, Innovative Center of RNA Medicine, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-7784","authenticated-orcid":false,"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"15Molecular and Cellular Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1298-7653","authenticated-orcid":false,"given":"Lewis C.","family":"Cantley","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"9Department of Cell Biology, Harvard Medical School, Boston, Massachusetts."},{"name":"10Meyer Cancer Center, Weill Cornell Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-3955","authenticated-orcid":false,"given":"Thomas M.","family":"Roberts","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-5688","authenticated-orcid":false,"given":"Jean J.","family":"Zhao","sequence":"additional","affiliation":[{"name":"3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"4Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"2026030203253862100_bib1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/2159-8290.CD-12-0003","article-title":"Functional characterization of an isoform-selective inhibitor of PI3K-p110beta as a potential anticancer agent","volume":"2","author":"Ni","year":"2012","journal-title":"Cancer Discov"},{"key":"2026030203253862100_bib2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12943-019-0954-x","article-title":"Targeting PI3K in cancer: mechanisms and advances in clinical trials","volume":"18","author":"Yang","year":"2019","journal-title":"Mol Cancer"},{"key":"2026030203253862100_bib3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41586-018-0343-4","article-title":"Suppression of insulin feedback enhances the efficacy of PI3K inhibitors","volume":"560","author":"Hopkins","year":"2018","journal-title":"Nature"},{"key":"2026030203253862100_bib4","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa1813904","article-title":"Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer","volume":"380","author":"Andr\u00e9","year":"2019","journal-title":"N Engl J Med"},{"key":"2026030203253862100_bib5","doi-asserted-by":"crossref","first-page":"ra3","DOI":"10.1126\/scisignal.1161577","article-title":"Phosphoinositide 3-kinase p110beta activity: key role in metabolism and mammary gland cancer but not development","volume":"1","author":"Ciraolo","year":"2008","journal-title":"Sci Signal"},{"key":"2026030203253862100_bib6","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1158\/1541-7786.MCR-21-0322","article-title":"Blocking PI3K p110\u03b2 attenuates development of PTEN-deficient castration-resistant prostate cancer","volume":"20","author":"Gao","year":"2022","journal-title":"Mol Cancer Res"},{"key":"2026030203253862100_bib7","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nature13948","article-title":"Convergent loss of PTEN leads to clinical resistance to a PI(3)K\u03b1 inhibitor","volume":"518","author":"Juric","year":"2015","journal-title":"Nature"},{"key":"2026030203253862100_bib8","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1158\/0008-5472.CAN-09-2525","article-title":"Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors","volume":"70","author":"Edgar","year":"2010","journal-title":"Cancer Res"},{"key":"2026030203253862100_bib9","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature07091","article-title":"Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis","volume":"454","author":"Jia","year":"2008","journal-title":"Nature"},{"key":"2026030203253862100_bib10","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1101\/gad.191973.112","article-title":"The p110\u03b1 and p110\u03b2 isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis","volume":"26","author":"Utermark","year":"2012","journal-title":"Genes Dev"},{"key":"2026030203253862100_bib11","doi-asserted-by":"crossref","first-page":"18443","DOI":"10.1073\/pnas.0508988102","article-title":"The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells","volume":"102","author":"Zhao","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026030203253862100_bib12","doi-asserted-by":"crossref","first-page":"8501","DOI":"10.1038\/ncomms9501","article-title":"A PI3K p110\u03b2-Rac signalling loop mediates Pten-loss-induced perturbation of haematopoiesis and leukaemogenesis","volume":"6","author":"Yuzugullu","year":"2015","journal-title":"Nat Commun"},{"key":"2026030203253862100_bib13","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41586-023-05940-w","article-title":"PI3K\u03b2 controls immune evasion in PTEN-deficient breast tumours","volume":"617","author":"Bergholz","year":"2023","journal-title":"Nature"},{"key":"2026030203253862100_bib14","doi-asserted-by":"crossref","first-page":"13057","DOI":"10.1073\/pnas.0802655105","article-title":"PTEN-deficient cancers depend on PIK3CB","volume":"105","author":"Wee","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026030203253862100_bib15","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/nar\/gkg141","article-title":"Functional studies of the PI(3)-kinase signalling pathway employing synthetic and expressed siRNA","volume":"31","author":"Czauderna","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2026030203253862100_bib16","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1158\/1078-0432.CCR-12-3815","article-title":"PI3K pathway dependencies in endometrioid endometrial cancer cell lines","volume":"19","author":"Weigelt","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2026030203253862100_bib17","doi-asserted-by":"crossref","first-page":"5981","DOI":"10.1158\/1078-0432.CCR-17-0725","article-title":"A first-time-in-human study of GSK2636771, a phosphoinositide 3 kinase beta-selective inhibitor, in patients with advanced solid tumors","volume":"23","author":"Mateo","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2026030203253862100_bib18","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.tibs.2009.02.003","article-title":"Twice upon a time: PI3K\u2019s secret double life exposed","volume":"34","author":"Hirsch","year":"2009","journal-title":"Trends Biochem Sci"},{"key":"2026030203253862100_bib19","first-page":"169","article-title":"Early embryonic lethality in mice deficient in the p110beta catalytic subunit of PI 3-kinase","volume":"13","author":"Bi","year":"2002","journal-title":"Mamm Genome"},{"key":"2026030203253862100_bib20","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1091\/mbc.e09-08-0744","article-title":"Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male fertility","volume":"21","author":"Ciraolo","year":"2010","journal-title":"Mol Biol Cell"},{"key":"2026030203253862100_bib21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrc3860","article-title":"PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting","volume":"15","author":"Thorpe","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"2026030203253862100_bib22","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1634\/theoncologist.2014-0228","article-title":"A phase I\/II study combining erlotinib and dasatinib for non-small cell lung cancer","volume":"19","author":"Gold","year":"2014","journal-title":"Oncologist"},{"key":"2026030203253862100_bib23","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/S1470-2045(13)70479-0","article-title":"Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial","volume":"14","author":"Araujo","year":"2013","journal-title":"Lancet Oncol"},{"key":"2026030203253862100_bib24","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ygyno.2021.01.022","article-title":"Dasatinib, paclitaxel, and carboplatin in women with advanced-stage or recurrent endometrial cancer: a pilot clinical and translational study","volume":"161","author":"Coleman","year":"2021","journal-title":"Gynecol Oncol"},{"key":"2026030203253862100_bib25","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.molcel.2018.09.031","article-title":"MYC protein interactome profiling reveals functionally distinct regions that cooperate to drive tumorigenesis","volume":"72","author":"Kalkat","year":"2018","journal-title":"Mol Cell"},{"key":"2026030203253862100_bib26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41586-022-04431-8","article-title":"Low-dose metformin targets the lysosomal AMPK pathway through PEN2","volume":"603","author":"Ma","year":"2022","journal-title":"Nature"},{"key":"2026030203253862100_bib27","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.molcel.2019.08.006","article-title":"PTEN suppresses glycolysis by dephosphorylating and inhibiting autophosphorylated PGK1","volume":"76","author":"Qian","year":"2019","journal-title":"Mol Cell"},{"key":"2026030203253862100_bib28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ccr.2009.04.009","article-title":"EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt","volume":"16","author":"Miao","year":"2009","journal-title":"Cancer Cell"},{"key":"2026030203253862100_bib29","doi-asserted-by":"crossref","first-page":"e1004846","DOI":"10.1371\/journal.ppat.1004846","article-title":"EphrinA2 receptor (EphA2) is an invasion and intracellular signaling receptor for Chlamydia trachomatis","volume":"11","author":"Subbarayal","year":"2015","journal-title":"PLoS Pathog"},{"key":"2026030203253862100_bib30","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/s41419-020-02831-0","article-title":"Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2\/Erk-1\/2 signaling pathway","volume":"11","author":"Xiang","year":"2020","journal-title":"Cell Death Dis"},{"key":"2026030203253862100_bib31","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.ccr.2012.11.005","article-title":"The EphA2 receptor drives self-renewal and tumorigenicity in stem-like tumor-propagating cells from human glioblastomas","volume":"22","author":"Binda","year":"2012","journal-title":"Cancer Cell"},{"key":"2026030203253862100_bib32","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1038\/onc.2017.170","article-title":"Targeting EphA2 impairs cell cycle progression and growth of basal-like\/triple-negative breast cancers","volume":"36","author":"Song","year":"2017","journal-title":"Oncogene"},{"key":"2026030203253862100_bib33","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1038\/s41388-021-01714-8","article-title":"Oncogenic functions and therapeutic targeting of EphA2 in cancer","volume":"40","author":"Wilson","year":"2021","journal-title":"Oncogene"},{"key":"2026030203253862100_bib34","doi-asserted-by":"crossref","first-page":"e2211927120","DOI":"10.1073\/pnas.2211927120","article-title":"ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth","volume":"120","author":"Zuo","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026030203253862100_bib35","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1158\/0008-5472.CAN-11-3605","article-title":"Activation of Ras\/PI3K\/ERK pathway induces c-Myc stabilization to upregulate argininosuccinate synthetase, leading to arginine deiminase resistance in melanoma cells","volume":"72","author":"Tsai","year":"2012","journal-title":"Cancer Res"},{"key":"2026030203253862100_bib36","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/90273","article-title":"Determination of protease cleavage site motifs using mixture-based oriented peptide libraries","volume":"19","author":"Turk","year":"2001","journal-title":"Nat Biotechnol"},{"key":"2026030203253862100_bib37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/nmeth708","article-title":"A rapid method for determining protein kinase phosphorylation specificity","volume":"1","author":"Hutti","year":"2004","journal-title":"Nat Methods"},{"key":"2026030203253862100_bib38","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1158\/2159-8290.CD-18-0830","article-title":"PTEN loss mediates clinical cross-resistance to CDK4\/6 and PI3K\u03b1 inhibitors in breast cancer","volume":"10","author":"Costa","year":"2020","journal-title":"Cancer Discov"},{"key":"2026030203253862100_bib39","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.immuni.2017.02.001","article-title":"Loss of PTEN is associated with resistance to anti-PD-1 checkpoint blockade therapy in metastatic uterine leiomyosarcoma","volume":"46","author":"George","year":"2017","journal-title":"Immunity"},{"key":"2026030203253862100_bib40","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1158\/2159-8290.CD-15-0283","article-title":"Loss of PTEN promotes resistance to T cell-mediated immunotherapy","volume":"6","author":"Peng","year":"2016","journal-title":"Cancer Discov"},{"key":"2026030203253862100_bib41","doi-asserted-by":"crossref","first-page":"4103","DOI":"10.1200\/JCO.24.00427","article-title":"US Food and Drug Administration approval summary: capivasertib with fulvestrant for hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with PIK3CA\/AKT1\/PTEN alterations","volume":"42","author":"Dilawari","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026030203253862100_bib42","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1056\/NEJMoa2214131","article-title":"Capivasertib in hormone receptor-positive advanced breast cancer","volume":"388","author":"Turner","year":"2023","journal-title":"N Engl J Med"},{"key":"2026030203253862100_bib43","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41586-021-03741-7","article-title":"EGFR activation limits the response of liver cancer to lenvatinib","volume":"595","author":"Jin","year":"2021","journal-title":"Nature"},{"key":"2026030203253862100_bib44","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.molcel.2018.01.001","article-title":"Nuclear receptor Nur77 facilitates melanoma cell survival under metabolic stress by protecting fatty acid oxidation","volume":"69","author":"Li","year":"2018","journal-title":"Mol Cell"},{"key":"2026030203253862100_bib45","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41586-022-05575-3","article-title":"An atlas of substrate specificities for the human serine\/threonine kinome","volume":"613","author":"Johnson","year":"2023","journal-title":"Nature"},{"key":"2026030203253862100_bib46","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41587-019-0344-3","article-title":"The functional landscape of the human phosphoproteome","volume":"38","author":"Ochoa","year":"2020","journal-title":"Nat Biotechnol"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-25-1126\/3670744\/cd-25-1126.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-25-1126\/3723300\/cd-25-1126.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/3\/521\/3740992\/cd-25-1126.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/3\/521\/3740992\/cd-25-1126.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T08:25:55Z","timestamp":1772439955000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/16\/3\/521\/774739\/PTEN-Loss-Promotes-PI3K-Phosphorylation-and-EPHA2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,11,17]]},"published-print":{"date-parts":[[2026,3,2]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-25-1126","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.31443518","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31443515","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.8332130","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]}}}