About: Quantitative proteomic profiling of pleiomorphic human sarcoma identifies CLIC1 as a dominant pro-oncogenic receptor expressed in diverse sarcoma types     Goto   Sponge   NotDistinct   Permalink

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Description
  • Sarcomas are rare forms of cancer with a high unmet clinical need that develop in connective tissue, such as muscle, bone, nerves, cartilage, and fat. The outcome for patients is poor, with surgery and postoperative radiotherapy the standard treatment for patients. A better understanding of the molecular pathology of sarcoma may allow for the development of novel therapeutics. There are dozens of sarcoma subtypes where there is a need for targetted therapeutics, with the most commonly studied including Ewing’s sarcoma and osteosarcoma. Here we initiate a proteomics-based target-discovery program to define „dominant“ pro-oncogenic signaling targets in the most common sarcoma in adults: high-grade pleiomorphic soft tissue sarcoma. We have carried out a proteome screen using tandem mass tag isobaric labeling on three high-grade undifferentiated pleomorphic sarcoma biopsies from different tissue sites. We identified the commonly dysregulated proteins within the three sarcomas and further validated the most penetrant receptor as CLIC1, using immunohistochemistry arising from two different population cohorts representing over 300 patients. The dominant expression of CLIC1 in a broad range of human sarcomas suggests that studying this relatively unexplored signaling pathway might provide new insights into disease mechanism and facilitate the development of new CLIC1 targeted therapeutics.
  • Sarcomas are rare forms of cancer with a high unmet clinical need that develop in connective tissue, such as muscle, bone, nerves, cartilage, and fat. The outcome for patients is poor, with surgery and postoperative radiotherapy the standard treatment for patients. A better understanding of the molecular pathology of sarcoma may allow for the development of novel therapeutics. There are dozens of sarcoma subtypes where there is a need for targetted therapeutics, with the most commonly studied including Ewing’s sarcoma and osteosarcoma. Here we initiate a proteomics-based target-discovery program to define „dominant“ pro-oncogenic signaling targets in the most common sarcoma in adults: high-grade pleiomorphic soft tissue sarcoma. We have carried out a proteome screen using tandem mass tag isobaric labeling on three high-grade undifferentiated pleomorphic sarcoma biopsies from different tissue sites. We identified the commonly dysregulated proteins within the three sarcomas and further validated the most penetrant receptor as CLIC1, using immunohistochemistry arising from two different population cohorts representing over 300 patients. The dominant expression of CLIC1 in a broad range of human sarcomas suggests that studying this relatively unexplored signaling pathway might provide new insights into disease mechanism and facilitate the development of new CLIC1 targeted therapeutics. (en)
Title
  • Quantitative proteomic profiling of pleiomorphic human sarcoma identifies CLIC1 as a dominant pro-oncogenic receptor expressed in diverse sarcoma types
  • Quantitative proteomic profiling of pleiomorphic human sarcoma identifies CLIC1 as a dominant pro-oncogenic receptor expressed in diverse sarcoma types (en)
skos:prefLabel
  • Quantitative proteomic profiling of pleiomorphic human sarcoma identifies CLIC1 as a dominant pro-oncogenic receptor expressed in diverse sarcoma types
  • Quantitative proteomic profiling of pleiomorphic human sarcoma identifies CLIC1 as a dominant pro-oncogenic receptor expressed in diverse sarcoma types (en)
skos:notation
  • RIV/00209805:_____/14:#0000514!RIV15-GA0-00209805
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(ED2.1.00/03.0101), P(GAP301/11/1678)
http://linked.open...iv/cisloPeriodika
  • 5
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 41097
http://linked.open...ai/riv/idVysledku
  • RIV/00209805:_____/14:#0000514
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • cancer; sarcoma; proteomics; receptor; pathology; CLIC1; CD44; CD63 (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [5873BF857AF2]
http://linked.open...i/riv/nazevZdroje
  • Journal of proteome research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 13
http://linked.open...iv/tvurceVysledku
  • Hernychová, Lenka
  • Vojtěšek, Bořivoj
  • Nekulová, Marta
  • Nenutil, Rudolf
http://linked.open...ain/vavai/riv/wos
  • 000335490600027
issn
  • 1535-3893
number of pages
http://bibframe.org/vocab/doi
  • 10.1021/pr4010713
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