PMID- 36184518
OWN - NLM
STAT- MEDLINE
DCOM- 20221004
LR  - 20221011
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 45
IP  - 10
DP  - 2022
TI  - SNAP23-Mediated Perturbation of Cholesterol-Enriched Membrane Microdomain 
      Promotes Extracellular Vesicle Production in Src-Activated Cancer Cells.
PG  - 1572-1580
LID - 10.1248/bpb.b22-00560 [doi]
AB  - Extracellular vesicles (EVs) originating from intraluminal vesicles (ILVs) formed 
      within multivesicular bodies (MVBs), often referred to as small EV (sEV) or 
      exosomes, are aberrantly produced by cancer cells and regulate the tumor 
      microenvironment. The tyrosine kinase c-Src is upregulated in a wide variety of 
      human cancers and is involved in promoting sEV secretion, suggesting its role in 
      malignant progression. In this study, we found that activated Src liberated 
      synaptosomal-associated protein 23 (SNAP23), a SNARE molecule, from lipid rafts 
      to non-rafts on cellular membrane. We also demonstrated that SNAP23 localized in 
      non-rafts induced cholesterol downregulation and ILV formation, resulting in the 
      upregulation of sEV production in c-Src-transformed cells. Furthermore, the 
      contribution of the SNAP23-cholesterol axis on sEV upregulation was confirmed in 
      pancreatic cancer cells. High SNAP23 expression is associated with poor prognosis 
      in patients with pancreatic cancer. These findings suggest a unique mechanism for 
      the upregulation of sEV production via SNAP23-mediated cholesterol downregulation 
      in Src-activated cancer cells.
FAU - Mitani, Fumie
AU  - Mitani F
AD  - Division of Cancer Cell Regulation, Aichi Cancer Center Research Institute.
AD  - Department of Oncology, Graduate School of Pharmaceutical Sciences, Nagoya City 
      University.
FAU - Hayasaka, Ryosuke
AU  - Hayasaka R
AD  - Institute for Advanced Biosciences, Keio University.
AD  - Systems Biology Program, Graduate School of Media and Governance, Keio 
      University.
FAU - Hirayama, Akiyoshi
AU  - Hirayama A
AD  - Institute for Advanced Biosciences, Keio University.
AD  - Systems Biology Program, Graduate School of Media and Governance, Keio 
      University.
AD  - Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, 
      Nagoya University.
FAU - Oneyama, Chitose
AU  - Oneyama C
AD  - Division of Cancer Cell Regulation, Aichi Cancer Center Research Institute.
AD  - Department of Oncology, Graduate School of Pharmaceutical Sciences, Nagoya City 
      University.
AD  - Department of Target and Drug Discovery, Graduate School of Medicine, Nagoya 
      University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Qb-SNARE Proteins)
RN  - 0 (Qc-SNARE Proteins)
RN  - 0 (SNAP23 protein, human)
RN  - 0 (SNARE Proteins)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Cholesterol/metabolism
MH  - *Exosomes/metabolism
MH  - Humans
MH  - Membrane Microdomains
MH  - *Pancreatic Neoplasms/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Qb-SNARE Proteins/genetics/metabolism
MH  - Qc-SNARE Proteins/genetics/metabolism
MH  - SNARE Proteins/metabolism
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - Src
OT  - cholesterol
OT  - intraluminal vesicle
OT  - raft
OT  - small extracellular vesicle
OT  - synaptosomal-associated protein 23
EDAT- 2022/10/03 06:00
MHDA- 2022/10/05 06:00
CRDT- 2022/10/02 22:19
PHST- 2022/10/02 22:19 [entrez]
PHST- 2022/10/03 06:00 [pubmed]
PHST- 2022/10/05 06:00 [medline]
AID - 10.1248/bpb.b22-00560 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2022;45(10):1572-1580. doi: 10.1248/bpb.b22-00560.