GOLGA2/GM130, cis-Golgi matrix protein, is a novel target of anticancer gene therapy.
Achievement of long-term survival of patients with lung cancer treated with conventional chemotherapy is still difficult for treatment of metastatic and advanced tumors. Despite recent progress in investigational therapies, survival rates are still disappointingly low and novel adjuvant and systemic therapies are urgently needed. A recently elucidated secretory pathway is attracting considerable interest as a promising anticancer target. The cis-Golgi matrix protein, GOLGA2/GM130, plays an important role in glycosylation and transport of protein in the secretory pathway. In this study, the effects of short hairpin RNA (shRNA) constructs targeting GOLGA2/GM130 (shGOLGA2) on autophagy and lung cancer growth were evaluated in vitro and in vivo. Downregulation of GOLGA2/GM130 led to induction of autophagy and inhibition of glycosylation in A549 cells and in the lungs of K-ras(LA1) mice. Furthermore, downregulation of GOLGA2/GM130 decreased angiogenesis and cancer cell invasion in vitro and suppressed tumorigenesis in lung cancer mice model. The tumor specificity of sequence targeting GOLGA2/GM130 was also demonstrated. Taken together, these results suggest that induction of autophagy by shGOLGA2 may induce cell death rather than cell survival. Therefore, downregulation of GOLGA2/GM130 may be a potential therapeutic option for lung cancer.
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Seung-Hee
SH
Chang
Seong-Ho
SH
Hong
Hu-Lin
HL
Jiang
Arash
A
Minai-Tehrani
Kyeong-Nam
KN
Yu
Jae-Ho
JH
Lee
Ji-Eun
JE
Kim
Ji-Young
JY
Shin
Bitna
B
Kang
Sungjin
S
Park
Kiwon
K
Han
Chanhee
C
Chae
Myung-Haing
MH
Cho
D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006031:Glycosylation; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000628:therapy; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D001324:Autoantigens; C097741:Golgin subfamily A member 2; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)