title: Cathepsin B is a target of Hedgehog signaling in pancreatic cancer.
abstract: This study investigated the influence of cathepsin B (CATB), a downstream target of Hedgehog (Hh) signaling, in pancreatic cancer. Cyclopamine (Hh signal inhibitor) suppressed expression of Shh, as well as Hh-induced transcription factor Gli1, and induced apoptosis in Shh-positive pancreatic cancer cell line (PANC-1). Microarray analysis revealed CATB as a gene downregulated by Hh. Cyclopamine reduced CATB protein and mRNA levels. Cyclopamine or CATB inhibitor reduced PANC-1 cell invasiveness (P<0.05). CATB expression in human pancreatic cancer tissues tended to correlate with Shh expression (P=0.053). Conclusively, Hh targets CATB and Hh signaling through CATB might influence pancreatic cancer cell invasiveness.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungon-dong Chongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Sang Hyub
authors.initials: SH
authors.lastname: Lee
authors.forename: Kwang Hyuck
authors.initials: KH
authors.lastname: Lee
authors.forename: Keung Youp
authors.initials: KY
authors.lastname: Lee
authors.forename: Haeryoung
authors.initials: H
authors.lastname: Kim
authors.forename: Ji Kon
authors.initials: JK
authors.lastname: Ryu
authors.forename: Yong Bum
authors.initials: YB
authors.lastname: Yoon
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002401:Cathepsin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D012333:RNA, Messenger; C509239:SHH protein, human; D002401:Cathepsin B