Details

Autor(en) / Beteiligte

• Babic, Ivan
• Anderson, Erik S.
• Tanaka, Kazuhiro
• Guo, Deliang
• Masui, Kenta
• Li, Bing
• Zhu, Shaojun
• Gu, Yuchao
• Villa, Genaro R.
• Akhavan, David
• Nathanson, David
• Gini, Beatrice
• Mareninov, Sergey
• Li, Rui
• Camacho, Carolina Espindola
• Kurdistani, Siavash K.
• Eskin, Ascia
• Nelson, Stanley F.
• Yong, William H.
• Cavenee, Webster K.
• Cloughesy, Timothy F.
• Christofk, Heather R.
• Black, Douglas L.
• Mischel, Paul S.

Titel

EGFR Mutation-Induced Alternative Splicing of Max Contributes to Growth of Glycolytic Tumors in Brain Cancer

Ist Teil von

• Cell metabolism, 2013-06, Vol.17 (6), p.1000-1008

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Alternative splicing contributes to diverse aspects of cancer pathogenesis including altered cellular metabolism, but the specificity of the process or its consequences are not well understood. We characterized genome-wide alternative splicing induced by the activating EGFRvIII mutation in glioblastoma (GBM). EGFRvIII upregulates the heterogeneous nuclear ribonucleoprotein (hnRNP) A1 splicing factor, promoting glycolytic gene expression and conferring significantly shorter survival in patients. HnRNPA1 promotes splicing of a transcript encoding the Myc-interacting partner Max, generating Delta Max, an enhancer of Myc-dependent transformation. Delta Max, but not full-length Max, rescues Myc-dependent glycolytic gene expression upon induced EGFRvIII loss, and correlates with hnRNPA1 expression and downstream Myc-dependent gene transcription in patients. Finally, Delta Max is shown to promote glioma cell proliferation in vitro and augment EGFRvIII expressing GBM growth in vivo. These results demonstrate an important role for alternative splicing in GBM and identify Delta Max as a mediator of Myc-dependent tumor cell metabolism. [Display omitted] •EGFRvIII regulates hnRNPA1 splicing factor expression in glioblastoma•HnRNPA1 promotes splicing of the Myc interacting protein Max to generate Delta Max•Delta Max promotes Myc-dependent glycolysis and tumor growth in vivo•HnRNPA1 and glycolytic gene expression correlate with poor patient survival