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However, the underlying mechanisms that govern lineage plasticity in carcinomas are undefined. Here in this study, we found that\n                    <jats:italic>PAX5<\/jats:italic>\n                    , a neural\/lymphatic transcription factor, contributed to neuroendocrine (NE) lineage transition.\n                    <jats:italic>PAX5<\/jats:italic>\n                    was highly expressed in aggressive human NE carcinoma cells and tissues but not in non-NE cancer cells and tissues. Deletion of\n                    <jats:italic>Pax5<\/jats:italic>\n                    in\n                    <jats:italic>\n                      Rb1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      Trp53\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice caused a reduction of tumor vessels, loss of NE morphologic features, and decreased expression of ASCL1, NCAM, and SYP, whereas ectopic expression of\n                    <jats:italic>PAX5<\/jats:italic>\n                    in CC10-rtTA TetO-\n                    <jats:italic>hEGFR<\/jats:italic>\n                    <jats:sup>ex19del\/T790M<\/jats:sup>\n                    mouse adenocarcinomas and in LNCAP prostate cancer xenografts induced an angiogenic microenvironment and NE morphology. Importantly, antiangiogenic drugs reduced NE features of\n                    <jats:italic>\n                      Rb1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      Trp53\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    tumors and blocked\n                    <jats:italic>PAX5<\/jats:italic>\n                    -induced NE transformation. These studies demonstrate an essential role of an angiogenic microenvironment in transition\/maintenance of NE lineage, suggesting that targeting\n                    <jats:italic>PAX5<\/jats:italic>\n                    and its downstream signaling may modulate lineage transitions responsible for treatment failure in both small cell neuroendocrine carcinoma and adenocarcinomas.\n                  <\/jats:p>","DOI":"10.1172\/jci190596","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:00:57Z","timestamp":1784822457000},"source":"Crossref","is-referenced-by-count":0,"title":["PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression"],"prefix":"10.1172","volume":"136","author":[{"given":"Ailing","family":"Wu","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Jiande Hospital, Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal 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