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The RhoJ-BAD signaling network: An Achilles’ heel for BRAF mutant melanomas
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نویسنده
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ruiz r. ,jahid s. ,harris m. ,marzese d.m. ,espitia f. ,vasudeva p. ,chen c.-f. ,de feraudy s. ,wu j. ,gillen d.l. ,krasieva t.b. ,tromberg b.j. ,pavan w.j. ,hoon d.s. ,ganesan a.k.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 7
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چکیده
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Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered. in this study,we identify a rhoj signaling pathway that is a selective therapeutic target for braf mutant cells. rhoj deletion in braf mutant melanocytes modulates the expression of the pro-apoptotic protein bad as well as genes involved in cellular metabolism,impairing nevus formation,cellular transformation,and metastasis. short-term treatment of nascent melanoma tumors with pak inhibitors that block rhoj signaling halts the growth of braf mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via a bad-dependent mechanism. as up to 50% of braf mutant human melanomas express high levels of rhoj,these studies nominate the rhoj-bad signaling network as a therapeutic vulnerability for fledgling braf mutant human tumors. © 2017 public library of science. all rights reserved.
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آدرس
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department of biological chemistry,university of california,irvine,irvine,ca, United States, department of dermatology,university of california,irvine,irvine,ca, United States, department of biology,the university of alabama at birmingham,birmingham,al, United States, national human genome research institute,national institute of health,bethesda,md, United States, department of dermatology,university of california,irvine,irvine,ca, United States, department of dermatology,university of california,irvine,irvine,ca, United States, department of dermatology,university of california,irvine,irvine,ca, United States, department of dermatology,university of california,irvine,irvine,ca, United States, department of biological chemistry,university of california,irvine,irvine,ca, United States, department of statistics,university of california,irvine,irvine,ca, United States, department of translational molecular medicine,division molecular oncology,john wayne cancer institute (jwci),providence saint john’s health center,santa monica,ca, United States, department of translational molecular medicine,division molecular oncology,john wayne cancer institute (jwci),providence saint john’s health center,santa monica,ca, United States, laser microbeam and medical program,beckman laser institute,university of california,15 irvine,irvine,ca, United States, national human genome research institute,national institute of health,bethesda,md, United States, department of biological chemistry,university of california,irvine,irvine,ca,united states,department of dermatology,university of california,irvine,irvine,ca, United States
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Authors
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