Tweety-Homolog 1 Drives Brain Colonization of Gliomas

• DOI: 10.1523/jneurosci.3532-16.2017
• Publication Date: 2017-06-13T00:30:33Z
• Authors: Erik Jung; Matthias Osswald; Jonas Blaes; Benedikt Wiestler; Felix Sahm; Torsten Schmenger; Gergely Solecki; Katrin Deumelandt; Felix T. Kurz; Ruifan Xie; Sophie Weil; Oliver Heil; Carina Thomé; Miriam Gömmel; Mustafa Syed; Peter Häring; Peter E. Huber; Sabine Heiland; Michael Platten; Andreas von Deimling; Wolfgang Wick; Frank Winkler
• Keywords: Radioresistance; Brain tumor

Early and progressive colonization of the healthy brain is one hallmark diffuse gliomas, including glioblastomas. We recently discovered ultralong (&gt;10 to hundreds microns) membrane protrusions [tumor microtubes (TMs)] extended by glioma cells. TMs have been associated with capacity cells effectively invade proliferate. Moreover, are also used some tumor interconnect large, resistant multicellular network. Here, we performed a correlative gene-expression microarray <i>in vivo</i> imaging analysis, identified novel molecular candidates for TM formation function. Interestingly, these genes were previously linked normal CNS development. One scoring highest in tests related outgrowth was <i>tweety-homolog 1</i> (<i>TTYH1</i>), which highly expressed fraction mice patients. Ttyh1 confirmed be potent regulator morphology TM-mediated tumor-cell invasion proliferation. Glioma or two mainly responsible effective colonization, downregulation particularly affected this cellular subtype, resulting reduced progression prolonged survival mice. The remaining Ttyh1-deficient cells, however, had more interconnecting TMs, increased radioresistance those small tumors. These findings imply heterogeneity gliomas regarding function distinct subtypes, multiple parallels neuronal development, suggest that might promising target specifically reduce TM-associated <b>SIGNIFICANCE STATEMENT</b> In report, identify tweety-homolog 1 (Ttyh1), protein as driver microtube (TM)-mediated Targeting inhibited invasive growth, but network intercellular suggesting functional potential implications future TM-targeting strategies.