The role of oncogenic RAC1 in melanoma initiation and progression

The role of oncogenic RAC1 in melanoma initiation and progression

RAC1P29S is the third most common mutation in human melanoma, after oncogenic BRAF and NRAS mutations. Here, we study the role of RAC1P29S in melanoma initiation and progression. Signalling studies and functional screening reveal that RAC1P29S activates PAK, AKT and the SRF/MRTF transcription factor...

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Main Author: Lionarons, Daniël Andreas
Published: University College London (University of London) 2018
Online Access:https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763221
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spelling ndltd-bl.uk-oai-ethos.bl.uk-7632212019-02-12T03:26:26ZThe role of oncogenic RAC1 in melanoma initiation and progressionLionarons, Daniël Andreas2018RAC1P29S is the third most common mutation in human melanoma, after oncogenic BRAF and NRAS mutations. Here, we study the role of RAC1P29S in melanoma initiation and progression. Signalling studies and functional screening reveal that RAC1P29S activates PAK, AKT and the SRF/MRTF transcription factor complex. Functionally, RAC1P29S promotes survival of cells deprived of growth factors or anchorage, linked to a gene expression profile that represents a melanocytic to mesenchymal transition. Mice with endogenous expression of RAC1P29S in the whole body develop lymphoma. When expressed only in melanocytes, RAC1P29S cooperates with oncogenic BRAF or with NF1-loss to promote tumourigenesis and resistance to BRAF inhibitors. These findings indicate that RAC1P29S is a melanoma driver oncogene and mediator of drug resistance, while identifying downstream effectors with potential for therapeutic targeting.University College London (University of London)https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763221http://discovery.ucl.ac.uk/10058450/Electronic Thesis or Dissertation
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sources NDLTD
description RAC1P29S is the third most common mutation in human melanoma, after oncogenic BRAF and NRAS mutations. Here, we study the role of RAC1P29S in melanoma initiation and progression. Signalling studies and functional screening reveal that RAC1P29S activates PAK, AKT and the SRF/MRTF transcription factor complex. Functionally, RAC1P29S promotes survival of cells deprived of growth factors or anchorage, linked to a gene expression profile that represents a melanocytic to mesenchymal transition. Mice with endogenous expression of RAC1P29S in the whole body develop lymphoma. When expressed only in melanocytes, RAC1P29S cooperates with oncogenic BRAF or with NF1-loss to promote tumourigenesis and resistance to BRAF inhibitors. These findings indicate that RAC1P29S is a melanoma driver oncogene and mediator of drug resistance, while identifying downstream effectors with potential for therapeutic targeting.
author Lionarons, Daniël Andreas
spellingShingle Lionarons, Daniël Andreas
The role of oncogenic RAC1 in melanoma initiation and progression
author_facet Lionarons, Daniël Andreas
author_sort Lionarons, Daniël Andreas
title The role of oncogenic RAC1 in melanoma initiation and progression
title_short The role of oncogenic RAC1 in melanoma initiation and progression
title_full The role of oncogenic RAC1 in melanoma initiation and progression
title_fullStr The role of oncogenic RAC1 in melanoma initiation and progression
title_full_unstemmed The role of oncogenic RAC1 in melanoma initiation and progression
title_sort role of oncogenic rac1 in melanoma initiation and progression
publisher University College London (University of London)
publishDate 2018
url https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763221
work_keys_str_mv AT lionaronsdanielandreas theroleofoncogenicrac1inmelanomainitiationandprogression
AT lionaronsdanielandreas roleofoncogenicrac1inmelanomainitiationandprogression
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