期刊
ONCOTARGET
卷 7, 期 40, 页码 65335-65347出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11678
关键词
lung cancer; gene therapy; endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3); golgi apparatus; ER stress
资金
- National Research Foundation - Ministry of Science, ICT & Future Planning [NRF-2012M3A9B6055302]
- Research Institute for Veterinary Science
- Seoul National University
- BK21 PLUS Program for Creative Veterinary Science Research
Trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus is elevated in cancer cells. Therefore, proteins of the ER-Golgi intermediate compartment (ERGIC) attract significant attention as targets for cancer treatment. Enhanced cancer cell growth and epithelial-mesenchymal transition by ERGICs correlates with poor-prognosis of lung cancer. This prompted us to assess whether knockdown of ERGIC3 may decrease lung cancer growth. To test the hypothesis, the effects of ERGIC3 short hairpin RNA (shERGIC3) on ER stress-induced cell death and lung tumorigenesis were investigated both in vitro and in vivo. Knockdown of ERGIC3 led to ER stress-induced autophagic cell death and suppression of proliferation in the A549 human lung cancer cell-line. Moreover, non-invasive aerosol-delivery of shERGIC3 using the biocompatible carrier glycerol propoxylate triacrylate and spermine (GPT-SPE) inhibited lung tumorigenesis in the K-rasLA1 murine model of lung cancer. Our data suggest that suppression of ERGIC3 could provide a framework for the development of effective lung cancer therapies.
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