uu.seUppsala University Publications
Change search
Refine search result
1 - 2 of 2
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Chen, Zhi Xiong
    et al.
    Ludwig Institute for Cancer Research Ltd., Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    Wallis, Karin
    Ludwig Institute for Cancer Research Ltd., Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    Fell, Stuart M
    Ludwig Institute for Cancer Research Ltd., Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    Sobrado, Veronica R
    Ludwig Institute for Cancer Research Ltd., Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    Hemmer, Marie C
    Ludwig Institute for Cancer Research Ltd., Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    Ramsköld, Daniel
    Department of Cell and Molecular Biology, Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    Hellman, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Sandberg, Rickard
    Department of Cell and Molecular Biology, Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    Kenchappa, Rajappa S
    Moffi tt Cancer Center, Neuro-Oncology Program, Tampa, Florida, USA.
    Martinson, Tommy
    Department of Clinical Genetics, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, Göteborg, Sweden.
    Johnsen, John I
    Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm.
    Kogner, Per
    Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm.
    Schlisio, Susanne
    Ludwig Institute for Cancer Research Ltd., Karolinska Institutet, Nobels väg 3, SE-17177, Stockholm, Sweden.
    RNA helicase A is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma2014In: Cancer Discovery, ISSN 2159-8274, E-ISSN 2159-8290, Vol. 4, no 4, p. 434-451Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin KIF1B as a 1p36.2 tumor suppressor. However, the mechanism of tumor suppression is unknown. We found that KIF1B isoform β (KIF1Bβ) interacts with RNA helicase A (DHX9), causing nuclear accumulation of DHX9, followed by subsequent induction of the proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma and neuroblastoma arise from neural crest progenitors that compete for growth factors such as nerve growth factor (NGF) during development. KIF1Bβ is required for developmental apoptosis induced by competition for NGF. We show that DHX9 is induced by and required for apoptosis stimulated by NGF deprivation. Moreover, neuroblastomas with chromosomal deletion of 1p36 exhibit loss of KIF1Bβ expression and impaired DHX9 nuclear localization, implicating the loss of DHX9 nuclear activity in neuroblastoma pathogenesis.

    SIGNIFICANCE: KIF1Bβ has neuroblastoma tumor-suppressor properties and promotes and requires nuclear-localized DHX9 for its apoptotic function by activating XAF1 expression. Loss of KIF1Bβ alters subcellular localization of DHX9 and diminishes NGF dependence of sympathetic neurons, leading to reduced culling of neural progenitors, and, therefore, might predispose to tumor formation.

  • 2. Watkins, Johnathan
    et al.
    Weekes, Daniel
    Shah, Vandna
    Gazinska, Patrycja
    Joshi, Shalaka
    Sidhu, Bhavna
    Gillett, Cheryl
    Pinder, Sarah
    Vanoli, Fabio
    Jasin, Maria
    Mayrhofer, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Isaksson, Anders
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Cheang, Maggie C. U.
    Mirza, Hasan
    Frankum, Jessica
    Lord, Christopher J.
    Ashworth, Alan
    Vinayak, Shaveta
    Ford, James M.
    Telli, Melinda L.
    Grigoriadis, Anita
    Tutt, Andrew N. J.
    Genomic Complexity Profiling Reveals That HORMAD1 Overexpression Contributes to Homologous Recombination Deficiency in Triple-Negative Breast Cancers2015In: Cancer Discovery, ISSN 2159-8274, E-ISSN 2159-8290, Vol. 5, no 5, p. 488-505Article in journal (Refereed)
    Abstract [en]

    Triple-negative breast cancers (TNBC) are characterized by a wide spectrum of genomic alterations, some of which might be caused by defects in DNA repair processes such as homologous recombination (HR). Despite this understanding, associating particular patterns of genomic instability with response to therapy has been challenging. Here, we show that allelic-imbalanced copy-number aberrations (AiCNA) are more prevalent in TNBCs that respond to platinum-based chemotherapy, thus providing a candidate predictive biomarker for this disease. Furthermore, we show that a high level of AiCNA is linked with elevated expression of a meiosis-associated gene, HORMAD1. Elevated HORMAD1 expression suppresses RAD51-dependent HR and drives the use of alternative forms of DNA repair, the generation of AiCNAs, as well as sensitizing cancer cells to HR-targeting therapies. Our data therefore provide a mechanistic association between HORMAD1 expression, a specific pattern of genomic instability, and an association with response to platinum-based chemotherapy in TNBC. SIGNIFICANCE: Previous studies have shown correlation between mutational "scars" and sensitivity to platinums extending beyond associations with BRCA1/2 mutation, but do not elucidate the mechanism. Here, a novel allele-specific copy-number characterization of genome instability identifies and functionally validates the inappropriate expression of the meiotic gene HORMAD1 as a driver of HR deficiency in TNBC, acting to induce allelic imbalance and moderate platinum and PARP inhibitor sensitivity with implications for the use of such "scars" and expression of meiotic genes as predictive biomarkers.

1 - 2 of 2
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf