biostudies-literatureGao JFundamental Research Funds for the Central UniversitiesClinical Research Innovation Plan of Shanghai General HospitalShanghai Education Development Foundation and Shanghai Municipal Education CommissionNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationShanghai Rising-Star Programe2415384https://www.ebi.ac.uk/biostudies/studies/S-EPMC12097036biostudies-literatureUnknown12(19)Chordoma, a rare mesenchymal malignancy, exhibits a high tendency to postoperative recurrence and poor prognosis. To date, its tumorigenic regulatory mechanisms remain elusive, leading to a lack of effective therapeutic targets and drug sensitivity indicators. Here, via transcriptome and proteome analyses, RAB3B is unveiled as a prominent oncogenic regulator in chordoma, with high expression and enhancer-associated transcriptional activity. Notably, RAB3B ablation attenuated the chordoma cell stemness and malignant biological properties in vivo and in vitro. Through determining the RAB3B-mediated program in chordoma, it is identified that it enhanced the phosphorylation of S6 specifically at S235/236 and directly bound to S6. Mechanistically, RAB3B physically interacted with phosphorylase Advanced science (Weinheim, Baden-Wurttemberg, Germany)RAB3B Dictates mTORC1/S6 Signaling in Chordoma and Predicts Response to mTORC1-Targeted Therapy.PMC1209703622120220616CTCCR-2021C0921QA140750082472786821731682021M7024858207320719CG2082073155Meng TSong DGao JSun WChang ZHuang RYin HLi YWang PHuang ZWang SZhang YXiao JSong SLin JJin JfalseRAB3B Dictates mTORC1/S6 Signaling in Chordoma and Predicts Response to mTORC1-Targeted Therapy.Chordoma, a rare mesenchymal malignancy, exhibits a high tendency to postoperative recurrence and poor prognosis. To date, its tumorigenic regulatory mechanisms remain elusive, leading to a lack of effective therapeutic targets and drug sensitivity indicators. Here, via transcriptome and proteome analyses, RAB3B is unveiled as a prominent oncogenic regulator in chordoma, with high expression and enhancer-associated transcriptional activity. Notably, RAB3B ablation attenuated the chordoma cell stemness and malignant biological properties in vivo and in vitro. Through determining the RAB3B-mediated program in chordoma, it is identified that it enhanced the phosphorylation of S6 specifically at S235/236 and directly bound to S6. Mechanistically, RAB3B physically interacted with phosphorylase 2025-01-01T00:00:00Z2025 May2026-06-01T22:21:30.342Z2026-05-22T03:07:55.577ZS-EPMC120970364013581510.1002/advs.202415384