10 May

New manuscript published – RhoA regulates translation of the Nogo-A decoy SPARC in white matter-invading glioblastomas

Picture from: Wirthschaft et al., Acta Neuropathol. 2019 (CC BY 4.0)

A collaborative effort lead by Björn Tews and supported by the research consortium ‘Systems Biology of the Unfolded Protein Response in Glioma’ (SUPR-G, generously funded by the BMBF in the framework of the e:med initiative) has resulted in a recent publication in Acta Neuropathologica that demonstrates a function of the peptide SPARC in migration and infiltrative growth of glioblastoma cells. SPARC production and secretion is enhanced via regulation of the UPR sensor IRE1 via AKT. SPARC secretion then prevents Nogo-A from inhibiting migration via RhoA. Advanced ultramicroscopy in undissected mouse brains reveals that gliomas require SPARC for invading into white matter structures and its depletion reduces tumor dissemination which significantly prolongs survival and improves response to cytostatic therapy. The discovery of a novel RhoA-IRE1 axis now provides a druggable target for interfering with SPARC production and underscores its therapeutic value. The full publiation can be accessed here.

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