Lymphoma Tumor Suppressor Enhances Growth of Brain Tumors

While the A20 protein (tumor necrosis factor, alpha-induced protein 3 or TNFAIP3) is known to be tumor suppressive in lymphoma, a recent study has found that in glioblastoma, an aggressive type of brain tumor, A20 acts as a potent tumor enhancer.

Glioblastoma is characterized by the presence of a specialized subset of cancer stem cells (glioblastoma stem cells or GSCs) that are resistant to chemotherapy and have the capacity to self-renew and propagate tumors. In the current study, investigators at the Cleveland Clinic (Ohio, USA) examined the role of A20 in GSCs to determine whether it might be a suitable target for new anti-cancer drugs.
They reported in the February 23, 2010, online edition of the journal PLoS Biology that inhibiting expression of the A20 gene with lentiviral-mediated delivery of short hairpin RNA (shRNA) reduced levels of A20 protein and decreased GSC growth and survival. Loss of A20 sensitized GSCs to TNF-alpha (tumor necrosis factor-alpha)-mediated apoptosis.

A computer search of glioblastoma patient genomic databases indicated that A20 overexpression and amplification was correlated with decreased chance of survival. In a mouse xenograft brain tumor model, lowering A20 levels in the transplanted human glioblastomas increased the length of time the animals were able to survive.

"Everyone recognizes the need to identify new cancer targets, and this may be achieved by studying subgroups of tumor cells. Using this technique, we identified A20 as an important target. However, we still have a lot of work to do before translation for patient therapies,” said first author Dr. Anita B. Hjelmeland, a stem cell researcher at the Cleveland Clinic.

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