ArgBP2-dependent signaling regulates pancreatic cell migration, adhesion, and tumorigenicity.
The poor prognosis of pancreatic cancer is due to rapid locoregional invasion, the early development of metastases, and the limited efficacy of current therapies. To date, none of the identified oncogenes and suppressors involved in this disease have led to efficient treatments. Here, we describe that the scaffold protein ArgBP2 is repressed during oncogenic transformation of the pancreas. We could show, using a pancreatic cancer cell line model, that this repression of ArgBP2 participates in the progression of this disease. Interestingly, in vitro analyses revealed that the antitumoral potential of ArgBP2 is linked to the control of cell adhesion and migration rather than to the regulation of cell proliferation or sensitivity to apoptosis. Moreover, we could detail part of the molecular mechanism responsible by identifying new ArgBP2-interacting proteins, and show that this function is partly achieved by the control of a WAVE/PTP-PEST/c-Abl signaling complex. These findings point to a new mechanism of pancreatic cancer progression leading to invasion and metastasis and suggest that the ArgBP2 signaling pathway could represent a new target for cancer therapy.
INSERM U.624, Marseille cedex 9, France.
David
D
Taieb
Julie
J
Roignot
Frédéric
F
André
Stéphane
S
Garcia
Bénédicte
B
Masson
Anne
A
Pierres
Juan-Lucio
JL
Iovanna
Philippe
P
Soubeyran
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D010957:Plasmids; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12 / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D046888:Tissue Array Analysis; D014162:Transfection; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D016601:RNA-Binding Proteins; C490755:SORBS2 protein, human; C114864:WASF1 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D050721:Proto-Oncogene Proteins c-cbl; C516738:PTPN12 protein, human; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; C067419:CBL protein, human