Truncated Glioma-Associated Oncogene Homolog 1 (tGLI1) Mediates Mesenchymal Glioblastoma via Transcriptional Activation of CD44

Cancer Research
Tadas K RimkusHui-Wen Lo

Abstract

The molecular pathways driving mesenchymal glioblastoma (GBM) are still not well understood. We report here that truncated glioma-associated oncogene homolog 1 (tGLI1) is a tumor-specific transcription factor that facilitates GBM growth, is enriched in the mesenchymal subtype of GBM and glioma stem cells (GSC), and promotes mesenchymal GSC by upregulating transcription of CD44. In an orthotopic GBM xenograft mouse model, tGLI1-overexpressing tumors grew more aggressively with increased proliferation and angiogenesis compared with control and GLI1-overexpressing xenografts. tGLI1 was highly expressed in GBM clinical specimens but undetectable in normal brains, whereas GLI1 was expressed in both tissues. A tGLI1 activation signature (tGAS) correlated with glioma grade, tumor angiogenesis, and poor overall survival, and GBMs with high tGAS were enriched with mesenchymal GBM/GSC gene signatures. Neurospheres contained increased levels of tGLI1, but not GLI1, compared with the monolayer culture; mesenchymal GSC expressed more tGLI1 than proneural GSC. Ectopic tGLI1 expression enhanced the ability of mesenchymal GSC to yield neurospheres in vitro and to form tumors in mouse brains. Selective tGLI1 knockdown reduced neurosphere format...Continue Reading

References

May 1, 1996·Molecular and Cellular Biology·J S MaltzmanJ G Monroe
Apr 16, 2005·Molecular Cancer Research : MCR·Waldemar Debinski, Denise M Gibo
May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher E PelloskiKenneth D Aldape
Jan 2, 2007·Current Biology : CB·Virginie ClementAriel Ruiz i Altaba
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·M E PrinceL E Ailles
Feb 7, 2007·Cancer Research·Chenwei LiDiane M Simeone
Aug 27, 2009·Cancer Research·Hui-Wen LoFrancis Ali-Osman
Jan 20, 2010·Journal of Molecular Cell Biology·Barbara Stecca, Ariel Ruiz i Altaba
Feb 13, 2010·Neuro-oncology·Howard ColmanKen Aldape
Mar 8, 2011·International Journal of Radiation Oncology, Biology, Physics·Yu-Jen ChenK S Clifford Chao
Nov 25, 2011·Science Signaling·Ariel Ruiz i Altaba
Jun 7, 2012·Cancer Letters·Barbara E StopschinskiDagmar Beier
May 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ping MaoIchiro Nakano
Mar 25, 2014·Seminars in Cell & Developmental Biology·Giuseppe BiamontiClaudia Ghigna
Jan 15, 2015·International Journal of Radiation Oncology, Biology, Physics·Jiancheng ZhouDalin He
Jun 26, 2015·Genes & Development·Justin D LathiaJeremy N Rich
Aug 6, 2016·Oncotarget·Sara FerlugaWaldemar Debinski
Sep 1, 2016·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Kelly L MooneyIsaac Yang
Nov 29, 2016·Oncogene·M KumazoeH Tachibana
Apr 26, 2017·British Journal of Cancer·Concetta Di MauroRoberto Bianco

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Citations

Aug 10, 2018·Future Medicinal Chemistry·Jaclyn J RenfrowRoy E Strowd
Jun 20, 2019·Cancer Science·Weiye LiangLihui Wang
Feb 23, 2020·British Journal of Pharmacology·Chongwu WangRuxiang Xu
Aug 31, 2019·Journal of Oncology·Carlos VelásquezJosé L Fernández-Luna
Mar 15, 2020·International Journal of Molecular Sciences·Shigemi KoyamaGoshi Shiota
Sep 23, 2020·Cells·Daniel DohenyHui-Wen Lo
Jan 16, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anna M Krichevsky, Erik J Uhlmann
Dec 29, 2020·Seminars in Cancer Biology·Md Sahab UddinGhulam Md Ashraf
Mar 20, 2021·Seminars in Cancer Biology·Rui ZhangSuling Liu
Sep 23, 2021·Journal of the National Comprehensive Cancer Network : JNCCN·Rofieda R AlwaqfiDeqin Ma

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