• Home
  • Search Results
  • WRAP53 promotes cancer cell survival and is a potential target for cancer therapy.

WRAP53 promotes cancer cell survival and is a potential target for cancer therapy.

Cell death & disease (2011-03-04)
S Mahmoudi, S Henriksson, L Farnebo, K Roberg, M Farnebo
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Horse Serum, Donor herd, USA origin, sterile-filtered, suitable for cell culture, suitable for hybridoma
Sigma-Aldrich
Horse Serum, Donor Herd, USA origin, Heat inactivated, sterile-filtered, suitable for cell culture
SAFC
Ham′s Nutrient Mixture F12, liquid
Sigma-Aldrich
Horse serum, liquid
Sigma-Aldrich
Horse Serum, USA origin, Donor herd, suitable for cell culture, suitable for hybridoma
SAFC
Ham′s Nutrient Mixture F12, liquid
Sigma-Aldrich
Anti-Survivin antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution