Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and beta-catenin stabilization.
Pancreatic cancer is a deadly disease characterized by late diagnosis and resistance to therapy. Much progress has been made in defining gene defects in pancreatic cancer, but a full accounting of its molecular pathogenesis remains to be provided. Here, we show that expression of the ataxia-telangiectasia group D complementing gene (ATDC), also called TRIM29, is elevated in most invasive pancreatic cancers and pancreatic cancer precursor lesions. ATDC promoted cancer cell proliferation in vitro and enhanced tumor growth and metastasis in vivo. ATDC expression correlated with elevated beta-catenin levels in pancreatic cancer, and beta-catenin function was required for ATDC's oncogenic effects. ATDC was found to stabilize beta-catenin via ATDC-induced effects on the Disheveled-2 protein, a negative regulator of glycogen synthase kinase 3beta in the Wnt/beta-catenin signaling pathway.
Wang
Lidong
L
Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Heidt
David G
DG
Lee
Cheong J
CJ
Yang
Huibin
H
Logsdon
Craig D
CD
Zhang
Lizhi
L
Fearon
Eric R
ER
Ljungman
Mats
M
Simeone
Diane M
DM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics*; D000072261:Dishevelled Proteins; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; C087296:TRIM29 protein, human; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin