Rab27

Rab27 (RAB27A / RAB27B、Ras-related protein Rab-27 family)

一行要約

Rab GTPase ファミリーに属する small GTPase で、後期エンドソーム / multivesicular endosome (MVE) の plasma membrane へのドッキングと膜融合を制御し、エクソソーム放出の rate-limiting step を担う。Rab27A は MVE の細胞辺縁への運搬、Rab27B は MVE の plasma membrane との docking に分担する非冗長的役割を持つ (Ostrowski et al. NatCellBiol 2010 で同定)。Bobrie らはマウス腫瘍株 (4T1, TS/A) で Rab27a / Rab27b の knockdown が腫瘍由来エクソソーム分泌を有意に減少させ、転移巣形成・微小環境の myeloid 細胞動員を抑制することを示し、エクソソーム仲介型転移ニッチ形成の pharmacological vulnerability を提示した (Bobrie et al. CancerRes 2012)。

主要エビデンス

エクソソーム放出の制御: Rab27A/B は effector である Slp4-a (SYTL4) や Munc13-4 と協調して MVE plasma membrane docking を担う。Rab27 ファミリーの活性化は GEF (MADD など) により制御され、Rab27 ノックダウンは exosome 分泌を顕著に減少させる。

腫瘍進展における役割: 高転移性腫瘍細胞では Rab27A/B 高発現が報告され、循環血中 EV 数の増加を伴う。Rab27 抑制は転移性 niche 形成を阻害する。

メカニズム

Rab27 GTPase cycle: GDP-bound (inactive) → GEF mediated GTP loading → MVE-associated active form → effector (Slp4-a, Munc13-4, Slac2, MyRIP) binding → cytoskeleton tethering / docking → SNARE-driven membrane fusion → ILV release as exosomes.

Rab27A / Rab27B 分担:

• Rab27A: MVE の cell periphery への transport (actin-mediated)
• Rab27B: docking / fusion 段階の rate-limiting

両者の二重 KD でエクソソーム分泌が顕著に低下する一方、片方単独 KD では partial reduction に留まる redundancy も存在。

関連エンティティ・概念

• Pathway: Exosome-biogenesis-pathway (ESCRT-dependent / -independent biogenesis)
• Tetraspanin family: CD9 / CD63 / CD81 — エクソソーム表面マーカー
• ESCRT machinery: TSG101 / ALIX — canonical biogenesis
• Concept: EV-mediated-intercellular-communication / EV-organotropism / Pre-metastatic-niche
• MOC: cancer-extracellular-vesicles

関連論文

直近 30 件のみ表示中 (関連 99 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Brain metastasis

• Xu et al. Cell 2026 — Unbiased niche labeling maps immune-excluded niche in bone metastasis

Basic-Extracellular vesicles

• Liu et al. ACSApplMaterInterfaces 2024 — Cell-specific impacts of surface coating composition on extracellular vesicle secretion
• Clancy et al. AnnuRevPathol 2023 — Tumor-derived extracellular vesicles multifunctional entities in the tumor microenvironment
• Shin et al. Biomaterials 2022 — Novel antitumor therapeutic strategy using CD4+ T cell-derived extracellular vesicles
• Zhongyu et al. BiomedPharmacother 2024 — Review of pre-metastatic niches induced by osteosarcoma-derived extracellular vesicles in lung metastasis A potential
• Tang et al. BrainRes 2023 — Activated neutrophil-derived exosomes contribute to blood-brain barrier damage and hemorrhagic transformation after
• Wang et al. CancerImmunolImmunother 2022 — Tumor derived exosomes drive pre-metastatic niche formation in lung via modulating CCL1 fibroblast and CCR8 Treg cell…
• Kalluri et al. Cell 2023 — The role of extracellular vesicles in cancer
• Wang et al. CellMetab 2023 — Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment
• Deng et al. CellRep 2024 — Extracellular-vesicle-packaged S100A11 from osteosarcoma cells mediates lung premetastatic niche formation by
• Lucotti et al. EMBOJ 2022 — Extracellular vesicles and particles impact the systemic landscape of cancer
• Jung et al. JExtracellVesicles 2022 — Reprogramming of T cell-derived small extracellular vesicles using IL2 surface engineering induces potent anti-cancer
• Leary et al. JExtracellVesicles 2022 — Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes
• Yates et al. JExtracellVesicles 2022 — In sickness and in health the functional role of extracellular vesicles in physiology and pathology in vivo part II
• Su et al. JExtracellVesicles 2023 — Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis
• Li et al. JExtracellVesicles 2026 — Exosomal oleic acid promotes lymphangiogenesis and nodal metastasis in cervical cancer via the AKTmTOR pathway
• Han et al. MolCancer 2022 — Exosome biogenesis machinery, regulation, and therapeutic implications in cancer
• Cai et al. MolCancer 2026 — Extracellular vesicles in solid tumors from tumor ecology to engineered therapeutics
• Radler et al. MolTher 2023 — Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading
• Wedge et al. NatCommun 2022 — Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy
• Xie et al. NatCommun 2022 — Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-beta type II receptor signaling
• Yu et al. NatCommun 2025 — Defective neutrophil-derived exosomes facilitate macrophage activation through miR-122-5p in Behcet’s disease
• Gong et al. NatMater 2024 — Tumour-derived small extracellular vesicles act as a barrier to therapeutic nanoparticle delivery
• Cheng et al. NatRevDrugDiscov 2022 — Therapeutically harnessing extracellular vesicles
• Wang et al. Nature 2023 — Tumour extracellular vesicles and particles induce liver metabolic dysfunction
• Giudice et al. SciTranslMed 2025 — Target antigen-displaying extracellular vesicles boost CAR T cell efficacy in cell and mouse models of neuroblastoma
• Hu et al. SemCancerBiol 2023 — Tumor-derived nanoseeds condition the soil for metastatic organotropism

Basic-Neutrophil and myeloid cell

• Chen et al. FrontImmunol 2022 — Roles of the exosomes derived from myeloid-derived suppressor cells in tumor immunity and cancer progression

Basic-Others

• Zhang et al. CancerCell 2026 — Cancer cachexia a tumor-driven disorder of whole-body homeostasis

Clinical-Novel modalities

• Navarre et al. NatCancer 2026 — Tumor irradiation promotes antigen dressing of dendritic cells to enhance CAR T cell persistence and efficacy in lung