title: Endoplasmic reticulum-Golgi intermediate compartment protein 3 knockdown suppresses lung cancer through endoplasmic reticulum stress-induced autophagy.
abstract: 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.
authors: Laboratory 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.|New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea.
authors: Seong-Ho
authors: SH
authors: Hong
authors: Laboratory 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.
authors: Seung-Hee
authors: SH
authors: Chang
authors: Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin 17104, Korea.
authors: Kyung-Cho
authors: KC
authors: Cho
authors: Laboratory 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.|Graduate Group of Tumor Biology, Seoul National University, Seoul 08826, Korea.
authors: Sanghwa
authors: S
authors: Kim
authors: Laboratory 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.
authors: Sungjin
authors: S
authors: Park
authors: Laboratory 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.
authors: Ah Young
authors: AY
authors: Lee
authors: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Hu-Lin
authors: HL
authors: Jiang
authors: Laboratory 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.
authors: Hyeon-Jeong
authors: HJ
authors: Kim
authors: Laboratory 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.|Graduate Group of Tumor Biology, Seoul National University, Seoul 08826, Korea.
authors: Somin
authors: S
authors: Lee
authors: Laboratory 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.
authors: Kyeong-Nam
authors: KN
authors: Yu
authors: Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
authors: Hwi Won
authors: HW
authors: Seo
authors: Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
authors: Chanhee
authors: C
authors: Chae
authors: Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin 17104, Korea.
authors: Kwang Pyo
authors: KP
authors: Kim
authors: Department of Pharmacology and Medical Science, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors: Jongsun
authors: J
authors: Park
authors: Laboratory 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.|Graduate Group of Tumor Biology, Seoul National University, Seoul 08826, Korea.|Graduate School of Convergence Science and Technology, Seoul National University, Suwon 16229, Korea.|Advanced Institute of Convergence Technology, Seoul National University, Suwon 16229, Korea.|Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun 25354, Korea.
authors: Myung-Haing
authors: MH
authors: Cho
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000235:genetics; D063646:Carcinogenesis; D048708:Cell Growth Processes; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D011905:Genes, ras; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C517615:ERGIC3 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt
keywords: ER stress; endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3); gene therapy; golgi apparatus; lung cancer