biostudies-literatureMartino FAssociazione Italiana per la Ricerca sul CancroMinistero della SaluteMinistero della Salute Ricerca Corrente: 2024-2025European Research CouncilItalian Ministry of University and Scientific Research grant PRIN 2020FPRC 5xmille Ministero Salute 2020Fondazione Piemontese per la Ricerca sul Cancro, FPRC 5xmille Ministero Salute 2017 PTCRC-INTRA 2020e02269https://www.ebi.ac.uk/biostudies/studies/S-EPMC12631847biostudies-literatureUnknown12(43)TBC1D22B is a GTPase-activating protein (GAP) associated with poor prognosis in breast cancer (BC). Using complementary proximity-labeling and co-immunoprecipitation proteomics, the TBC1D22B interactome in BC cells is defined, revealing strong enrichment in components of the ER-to-Golgi trafficking machinery, endosomal transport, and adhesion-related pathways. Functional assays, using the Retention Using Selective Hooks (RUSH) system, demonstrate that TBC1D22B inhibits ER-to-Golgi transport in a GAP-dependent manner. Mechanistic studies identify RAB1B as a direct target of TBC1D22B, and RAB1B silencing phenocopies the trafficking defects caused by TBC1D22B overexpression. In 3D culture, TBC1D22B promotes spheroid growth in a manner dependent on its GAP activity and not replicated by its paAdvanced science (Weinheim, Baden-Wurttemberg, Germany)TBC1D22B Regulates ER-to-Golgi Trafficking via RAB1B Inactivation and Promotes Oncogenic Programs in Breast Cancer.PMC1263184722811PRO-ACTIVEPNRR-MCNT2-2023-12378490 Next Generation EU2020R2BP2EERC-CoG2020 1010022802022W93FTWprojectSEE-HER10100228024415Martino FFreddi SMurabito APennisi RBussolino FBedin FMatoskova BBoncompain GSigismund SLanzetti LCuomo ALupi MFontana SFardin APerez FVillari GAndreoli LfalseTBC1D22B Regulates ER-to-Golgi Trafficking via RAB1B Inactivation and Promotes Oncogenic Programs in Breast Cancer.TBC1D22B is a GTPase-activating protein (GAP) associated with poor prognosis in breast cancer (BC). Using complementary proximity-labeling and co-immunoprecipitation proteomics, the TBC1D22B interactome in BC cells is defined, revealing strong enrichment in components of the ER-to-Golgi trafficking machinery, endosomal transport, and adhesion-related pathways. Functional assays, using the Retention Using Selective Hooks (RUSH) system, demonstrate that TBC1D22B inhibits ER-to-Golgi transport in a GAP-dependent manner. Mechanistic studies identify RAB1B as a direct target of TBC1D22B, and RAB1B silencing phenocopies the trafficking defects caused by TBC1D22B overexpression. In 3D culture, TBC1D22B promotes spheroid growth in a manner dependent on its GAP activity and not replicated by its pa2025-01-01T00:00:00Z2025 Nov2026-06-05T17:21:29.812Z2026-05-19T03:11:57.39ZS-EPMC126318474087843910.1002/advs.202502269