VAMP8, a vesicle-SNARE required for RAB37-mediated exocytosis, possesses a tumor metastasis suppressor function

We previously identified a metastasis suppressor RAB37 small GTPase that regulated exocytosis of tissue inhibitor of metalloproteinases 1 (TIMP1) to suppress lung cancer metastasis. Here, we show that vesicle-associated membrane protein 8 (VAMP8), a v-SNARE (vesicle soluble N-ethylmaleimide-sensitiv...

Full description

Saved in:
Bibliographic Details
Published in:Cancer letters 2018-11, Vol.437, p.79-88
Main Authors: Wang, Yu-Shiuan, Tzeng, Hong-Tai, Tsai, Chung-Han, Cheng, Hung-Chi, Lai, Wu-Wei, Liu, Hsiao-Sheng, Wang, Yi-Ching
Format: Article
Language:English
Subjects:
Exocytosis
Fluorescence
Guanosine triphosphatases
Immunoglobulins
Insulin
Lung cancer
Medical prognosis
Membrane proteins
Metastases
Metastasis
Motility
Multivariate analysis
N-Ethylmaleimide-sensitive protein
Prognosis
Protein expression
Proteins
RAB37
Regression analysis
Secretion
Signal transduction
SNAP receptors
Software
Survival
TIMP1
Tissue inhibitor of metalloproteinase 1
VAMP8
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We previously identified a metastasis suppressor RAB37 small GTPase that regulated exocytosis of tissue inhibitor of metalloproteinases 1 (TIMP1) to suppress lung cancer metastasis. Here, we show that vesicle-associated membrane protein 8 (VAMP8), a v-SNARE (vesicle soluble N-ethylmaleimide-sensitive factor activating protein receptor), interacts with RAB37 and drives the secretion of TIMP1 to inhibit tumor metastases. Confocal and total internal reflection fluorescence microscopic images demonstrated that VAMP8 co-localized with RAB37 and facilitated trafficking of RAB37-TIMP1 vesicles. Reconstitution experiments using tail-vein injection and lung-to-lung metastasis in mice showed that VAMP8 was essential for RAB37-regulated vesicle trafficking of TIMP1 to suppress cancer metastasis. Lung cancer patients with low VAMP8 showed distant metastasis, poor overall survival and progression-free survival. Importantly, multivariate Cox regression analysis indicated that patients with low VAMP8/low RAB37 expression profile showed significantly high risk of death (hazard ratio = 3.42, P 
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2018.08.023