Documents

DOI

  • Author: Lee, Alvin J. X.

    Cancer Research UK London Research Institute, United Kingdom

  • Author: Roylance, Rebecca

    Barts Cancer Institute, Queen Mary University of London, United Kingdom

  • Author: Sander, Jil

    Cancer Research UK, London Research Institute, United Kingdom

  • Author: Gorman, Patricia

    Barts Cancer Institute, Queen Mary University of London, United Kingdom

  • Author: Endesfelder, David

    Cancer Research UK, London Research Institute, United Kingdom

  • Author: Kschischo, Maik

    University of Applied Sciences Koblenz, RheinAhrCampus, Germany

  • Author: Jones, Neil P.

    University College London, United Kingdom

  • Author: East, Philip

    Cancer Research UK London Research Institute, United Kingdom

  • Author: Nicke, Barbara

    Cancer Research UK, London Research Institute, United Kingdom

  • Author: Spassieva, Stefka

    Department of Medicine, Medical University of South Carolina, United Kingdom

  • Author: Obeid, Lina M.

    Department of Medicine, Medical University of South Carolina, United Kingdom

  • Author: Birkbak, Nicolai Juul

    Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800, Lyngby, Denmark

  • Author: Szallasi, Zoltan

    Department of Systems Biology, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: McKnight, Nicole C.

    Cancer Research UK, London Research Institute, United Kingdom

  • Author: Rowan, Andrew J.

    Cancer Research UK, London Research Institute, United Kingdom

  • Author: Speirs, Valerie

    University of Leeds, United Kingdom

  • Author: Hanby, Andrew M.

    University of Leeds, United Kingdom

  • Author: Downward, Julian

    Cancer Research UK, London Research Institute, United Kingdom

  • Author: Tooze, Sharon A.

    Cancer Research UK, London Research Institute, United Kingdom

  • Author: Swanton, Charles

    Cancer Research UK, London Research Institute, United Kingdom

View graph of relations

Chromosomal instability (CIN) has been implicated in multidrug resistance and the silencing of the ceramide transporter, CERT, promotes sensitization to diverse cytotoxics. An improved understanding of mechanisms governing multidrug sensitization might provide insight into pathways contributing to the death of CIN cancer cells. Using an integrative functional genomics approach, we find that CERT‐specific multidrug sensitization is associated with enhanced autophagosome–lysosome flux, resulting from the expression of LAMP2 following CERT silencing in colorectal and HER2+ breast cancer cell lines. Live cell microscopy analysis revealed that CERT depletion induces LAMP2‐dependent death of polyploid cells following exit from mitosis in the presence of paclitaxel. We find that CERT is relatively over‐expressed in HER2+ breast cancer and CERT protein expression acts as an independent prognostic variable and predictor of outcome in adjuvant chemotherapy‐treated patients with primary breast cancer. These data suggest that the induction of LAMP2‐dependent autophagic flux through CERT targeting may provide a rational approach to enhance multidrug sensitization and potentiate the death of polyploid cells following paclitaxel exposure to limit the acquisition of CIN and intra‐tumour heterogeneity. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Original languageEnglish
JournalJournal of Pathology
Publication date2012
Volume226
Issue3
Pages482-494
ISSN0022-3417
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 11
Download as:
Download as PDF
Select render style:
APAAuthorCBEHarvardMLAStandardVancouverShortLong
PDF
Download as HTML
Select render style:
APAAuthorCBEHarvardMLAStandardVancouverShortLong
HTML
Download as Word
Select render style:
APAAuthorCBEHarvardMLAStandardVancouverShortLong
Word

Download statistics

No data available

ID: 23335837