title: TP53 transcription factor for the NEDD9/HEF1/Cas-L gene: potential targets in Non-Small Cell Lung Cancer treatment.
abstract: Lung cancer is a serious public health problem. Although there has been significant progress in chemotherapy, non-small cell lung cancer is still resistant to current treatments, primarily because of the slow rate of cell development. It is thus important to find new molecules directed against targets other than proliferation agents. Considering the high proportion of mutant proteins in tumor cells, and the high rate of mutation of the TP53 gene in all cancers, and in NSCLC in particular, this gene is a perfect target. Certain new molecules have been shown to restore the activity of mutated p53 protein, for example PRIMA-1, which reactivates the His273 mutant p53. In a previous study, we presented triazine A190, a molecule with a cytostatic activity that blocks cells in the G1 phase and induces apoptosis. Here, we show that A190 not only restores mutant p53 activity, but also induces an overexpression of the NEDD9 gene, leading to apoptotic death. These findings might offer hope for the development of new targeted therapies, specific to tumor cells, which spare healthy cells.
authors.affiliation: IICiMED/EA 1155 - Département Cancer du Poumon et Cibles Moléculaires, UFR Sciences Pharmaceutiques - 9 rue Bias - BP53508 - 44035 NANTES CEDEX 1 - FRANCE.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Rousseau
authors.affiliation: IICiMED/EA 1155 - Département Cancer du Poumon et Cibles Moléculaires, UFR Sciences Pharmaceutiques - 9 rue Bias - BP53508 - 44035 NANTES CEDEX 1 - FRANCE.
authors.forename: Catherine
authors.initials: C
authors.lastname: Jacquot
authors.affiliation: IICiMED/EA 1155 - Département Cancer du Poumon et Cibles Moléculaires, UFR Sciences Pharmaceutiques - 9 rue Bias - BP53508 - 44035 NANTES CEDEX 1 - FRANCE.
authors.forename: Julie
authors.initials: J
authors.lastname: Le Palabe
authors.affiliation: UMR INSERM U 1085 Groupe "Death receptors and tumor escape" - Université de Rennes 1 Campus Santé - Bâtiment 5 - 2 avenue du Prof Léon Bernard - 35043 RENNES - France.
authors.forename: Marine
authors.initials: M
authors.lastname: Malleter
authors.affiliation: IICiMED/EA 1155 - Département Cancer du Poumon et Cibles Moléculaires, UFR Sciences Pharmaceutiques - 9 rue Bias - BP53508 - 44035 NANTES CEDEX 1 - FRANCE.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tomasoni
authors.affiliation: IICiMED/EA 1155 - Département Cancer du Poumon et Cibles Moléculaires, UFR Sciences Pharmaceutiques - 9 rue Bias - BP53508 - 44035 NANTES CEDEX 1 - FRANCE.
authors.forename: Tifenn
authors.initials: T
authors.lastname: Boutard
authors.affiliation: IICiMED/EA 1155 - Département Cancer du Poumon et Cibles Moléculaires, UFR Sciences Pharmaceutiques - 9 rue Bias - BP53508 - 44035 NANTES CEDEX 1 - FRANCE.
authors.forename: Vehary
authors.initials: V
authors.lastname: Sakanyan
authors.affiliation: IICiMED/EA 1155 - Département Cancer du Poumon et Cibles Moléculaires, UFR Sciences Pharmaceutiques - 9 rue Bias - BP53508-44035 NANTES CEDEX 1-FRANCE.
authors.forename: Christos
authors.initials: C
authors.lastname: Roussakis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014227:Triazines / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C532394:4,6-diamino-1,2-dihydro-1-(4''-chlorophenyl)-2-(1-tricyclo(3.3.1.1(3,4)) decyl-1,3,5-triazine); D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C099942:NEDD9 protein, human; D009419:Nerve Tissue Proteins; C446290:PRIMA1 protein, human; D010750:Phosphoproteins; D014227:Triazines; D016159:Tumor Suppressor Protein p53