Cathepsin B is a target of Hedgehog signaling in pancreatic cancer.
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.
Hwang
Jin-Hyeok
JH
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.
Lee
Sang Hyub
SH
Lee
Kwang Hyuck
KH
Lee
Keung Youp
KY
Kim
Haeryoung
H
Ryu
Ji Kon
JK
Yoon
Yong Bum
YB
Kim
Yong-Tae
YT
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
D053823:Hedgehog Proteins; D012333:RNA, Messenger; C509239:SHH protein, human; D002401:Cathepsin B