WRAP53 Promotes Cancer Cell Survival and is a Potential Target for Cancer Therapy

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2011 Mar 4

PMID 21368886

Citations 38

Authors

S Mahmoudi

S Henriksson

L Farnebo

K Roberg

M Farnebo

Affiliations

Soon will be listed here.

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.

Citing Articles

Predicting Early Death in Head and Neck Cancer-A Pilot Study.

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Small Molecules Blocking the Assembly of TCAB1 and Telomerase Complexes: Lead Discovery and Biological Activity.

Zuo H, Ru Y, Gao X, Chen H, Yan Y, Ma X ACS Med Chem Lett. 2024; 15(8):1205-1212.

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Osteosarcoma Multi-Omics Landscape and Subtypes.

Tang S, Roberts R, Cheng L, Li L Cancers (Basel). 2023; 15(20).

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Predicting regional somatic mutation rates using DNA motifs.

Liu C, Wang Z, Wang J, Liu C, Wang M, Ngo V PLoS Comput Biol. 2023; 19(10):e1011536.

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The role of UCA1 and WRAP53 in diagnosis of hepatocellular carcinoma: A single-center case-control study.

Abdelmoety A, Elhassafy M, Said R, Elsheaita A, Mahmoud M Clin Exp Hepatol. 2023; 9(2):129-137.

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