@article{ff0b26e079cd443b836201631ac5722e,
title = "Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis",
abstract = "Rab small GTPases are master regulators of membrane trafficking and guide vesicle targeting. Recent publications show that Rab-controlled trafficking pathways are altered during tumorigenesis. However, whether any of the Rabs plays a metastasis suppressor role is least explored. Here we address the metastasis suppressive function of human Rab37 (hRAB37) using secretomics, cell, animal and clinical analyses. We show that tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted glycoprotein that inhibits extracellular matrix turnover, is a novel cargo of hRAB37. hRAB37 regulates the exocytosis of TIMP1 in a nucleotide-dependent manner to inactivate matrix metalloproteinase 9 (MMP9) migration axis in vitro and in vivo. Dysfunction of hRAB37 or TIMP1 abrogates metastasis suppression. Lung cancer patients with metastasis and poor survival show low hRAB37 protein expression coinciding with low TIMP1 in tumours. Our findings identify hRAB37 as a novel metastasis suppressor Rab that functions through the TIMP1-MMP9 pathway and has significant prognostic power.",
author = "Tsai, {Chung Han} and Cheng, {Hung Chi} and Wang, {Yu Shiuan} and Pinpin Lin and Jayu Jen and Kuo, {I. Ying} and Chang, {Ying Hua} and Liao, {Pao Chi} and Chen, {Ruey Hwa} and Yuan, {Wei Chien} and Hsu, {Han Shui} and Yang, {Muh Hwa} and Hsu, {Ming Ta} and Wu, {Chu Yi} and Wang, {Yi Ching}",
note = "Funding Information: We thank the transmission electron microscope core, Department of Pathology, National Cheng Kung University Hospital for providing technical support and Taiwan Bioinfor-matics Core at the National Cheng Kung University, supported by a National Science Council for assisting with MetaCore analyses. We acknowledge Dr Mien-Chie Hung and Dr Yi-Hsin Hsu, Department of Molecular and Cellular Oncology at MD Anderson Cancer Center, Dr Nan-Shan Chang, Institute of Molecular Medicine at National Cheng Kung University and Dr Chia-Jung Yu, Department of Biochemistry and Molecular Biology at Chang-Gung University for discussion and comments on the manuscript, Dr Hsueh-Fen Juan, Department of Molecular and Cellular Biology at National Taiwan University for GO analysis of secretomic proteins and Mr Tseng-Wei Wang and Mr Ming-Hsien Tsai at NHRI for their technical support. This work was supported by Taiwan Ministry of Science and Technology (103-2627-B-006-007), Taiwan National Health Research Institutes (EX103-10202BI) and Taiwan Ministry of Health and Welfare (103-TDU-PB-211-133005).",
year = "2014",
month = sep,
day = "3",
doi = "10.1038/ncomms5804",
language = "English",
volume = "5",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}