Endoplasmic reticulum-Golgi intermediate compartment protein 3 knockdown suppresses lung cancer through endoplasmic reticulum stress-induced autophagy
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Seong-Ho Hong1,2, Seung-Hee Chang1, Kyung-Cho Cho3, Sanghwa Kim1,4, Sungjin Park1, Ah Young Lee1, Hu-Lin Jiang5, Hyeon-Jeong Kim1, Somin Lee1,4, Kyeong-Nam Yu1, Hwi Won Seo6, Chanhee Chae6, Kwang Pyo Kim3, Jongsun Park7, Myung-Haing Cho1,4,8,9,10
1Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
2New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
3Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin 17104, Korea
4Graduate Group of Tumor Biology, Seoul National University, Seoul 08826, Korea
5Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China
6Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
7Department of Pharmacology and Medical Science, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea
8Graduate School of Convergence Science and Technology, Seoul National University, Suwon 16229, Korea
9Advanced Institute of Convergence Technology, Seoul National University, Suwon 16229, Korea
10Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun 25354, Korea
Myung-Haing Cho, email: firstname.lastname@example.org
Jongsun Park, email: email@example.com
Keywords: lung cancer, gene therapy, endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3), golgi apparatus, ER stress
Received: February 01, 2016 Accepted: August 08, 2016 Published: August 29, 2016
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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