VAV1: a new target in pancreatic cancer?
Pancreatic ductal adenocarcinoma (PDA) is arguably the most lethal malignancy in the United States. Despite the identification of many molecular alterations in PDA, this information has not translated into effective therapeutic strategies to date. A recent report in Cancer Cell (Fernandez-Zapico et al, Cancer Cell 2005, 7:39-49) reveals an unexpected role for the hematopoietic-specific RhoGEF VAV1 in pancreatic tumorigenesis, where ectopic expression of VAV1 as a result of promoter demethylation was identified in the majority of established cell lines and PDA tissue samples. Importantly, VAV1 expression was functionally required for optimal proliferation, transformation and survival of pancreatic cancer cell lines. This study provides the first evidence of VAV1 promoter demethylation as an event in cancer progression, suggesting that aberrant signaling pathways driven by VAV1 are potential therapeutic targets in PDA.
Denicola
Gina
G
Department of Cancer Biology, Abramson Family Cancer Research Institute, The Abramson Cancer Center at the University of Pennsylvania Medical Center, Philadelphia, PA, USA.
Tuveson
David A
DA
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D019175:DNA Methylation; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D051567:Proto-Oncogene Proteins c-vav; D012333:RNA, Messenger; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; D004815:Epidermal Growth Factor; D020830:rac1 GTP-Binding Protein