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WRAP53 promotes cancer cell survival and is a potential target for cancer therapy
Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
Karolinska Institute.
2011 (English)In: CELL DEATH and DISEASE, ISSN 2041-4889, Vol. 2, no e114Article in journal (Refereed) Published
Abstract [en]

We previously identified WRAP53 as an antisense transcript that regulates the p53 tumor suppressor. The WRAP53 gene also encodes a protein essential for Cajal body formation and involved in cellular trafficking of the survival of motor neuron complex, the telomerase enzyme and small Cajal body-specific RNAs to Cajal bodies. Here, we show that the WRAP53 protein is overexpressed in a variety of cancer cell lines of different origin and that WRAP53 overexpression promotes cellular transformation. Knockdown of the WRAP53 protein triggers massive apoptosis through the mitochondrial pathway, as demonstrated by Bax/Bak activation, loss of mitochondrial membrane potential and cytochrome c release. The apoptosis induced by WRAP53 knockdown could moreover be blocked by Bcl-2 overexpression. Interestingly, human tumor cells are more sensitive to WRAP53 depletion as compared with normal human cells indicating that cancer cells in particular depends on WRAP53 expression for their survival. In agreement with this, we found that high levels of WRAP53 correlate with poor prognosis of head and neck cancer. Together these observations propose a role of WRAP53 in carcinogenesis and identify WRAP53 as a novel molecular target for a large fraction of malignancies.

Place, publisher, year, edition, pages
Nature Publishing Group , 2011. Vol. 2, no e114
Keyword [en]
WRAP53, Wdr79, TCAB1, mitochondrial-dependent apoptosis, oncogene, head and neck cancer
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-65955DOI: 10.1038/cddis.2010.90ISI: 000286621400003OAI: oai:DiVA.org:liu-65955DiVA: diva2:400664
Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2014-09-23

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Roberg, Karin
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Oto-Rhiono-Laryngology and Head & Neck SurgeryFaculty of Health SciencesDepartment of ENT - Head and Neck Surgery UHL
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