Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling.
Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling.
BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736, Republic of Korea.
Sirichat
S
Kaowinn
BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736, Republic of Korea.
Il-Rae
IR
Cho
BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736, Republic of Korea.
Jeong
J
Moon
BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736, Republic of Korea.
Seung Won
SW
Jun
BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736, Republic of Korea.
Chang Seok
CS
Kim
Department of Microbiology, Pusan National University, Busan 609-736, Republic of Korea.
Ho Young
HY
Kang
Department of Medical Science, Dankook University College of Medicine, Cheonan 330-714, Republic of Korea.
Manbok
M
Kim
Department of Biological Sciences, Dong-A University, Busan 604-714, Republic of Korea.
Sang Seok
SS
Koh
BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736, Republic of Korea. Electronic address: younghc@pusan.ac.kr.
Young-Hwa
YH
Chung
D017209:Apoptosis; D045744:Cell Line, Tumor; D015870:Gene Expression; D052661:H-1 parvovirus; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050130:Oncolytic Virotherapy; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D010322:Parvoviridae Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
C507964:IFNAR1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C517340:ZG16B protein, human; D053633:Receptor, Interferon alpha-beta; D053634:TYK2 Kinase; C070139:TYK2 protein, human
H-1 virus; IFNAR; PAUF; Stat1; Tyk2