MET signaling regulates glioblastoma stem cells

Kyeung Min Joo, Juyoun Jin, Eunhee Kim, Kang Ho Kim, Yonghyun Kim, Bong Gu Kang, Youn Jung Kang, Justin D. Lathia, Kwang Ho Cheong, Paul H. Song, Hyunggee Kim, Ho Jun Seol, Doo Sik Kong, Jung Il Lee, Jeremy N. Rich, Jeongwu Lee, Do Hyun Nam

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Abstract

Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM. Here, we identified a distinct fraction of cells expressing a high level ofMET in human primaryGBMspecimens that were preferentially localized in perivascular regions of human GBM biopsy tissues and were found to be highly clonogenic, tumorigenic, and resistant to radiation. Inhibition of MET signaling in GSCs disrupted tumor growth and invasiveness both in vitro and in vivo, suggesting that MET activation is required for GSCs. Together, our findings indicate that MET activation in GBM is a functional requisite for the cancer stem cell phenotype and a promising therapeutic target.

Original languageEnglish
Pages (from-to)3828-3838
Number of pages11
JournalCancer Research
Volume72
Issue number15
DOIs
Publication statusPublished - 2012 Aug 1

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Joo, K. M., Jin, J., Kim, E., Kim, K. H., Kim, Y., Kang, B. G., Kang, Y. J., Lathia, J. D., Cheong, K. H., Song, P. H., Kim, H., Seol, H. J., Kong, D. S., Lee, J. I., Rich, J. N., Lee, J., & Nam, D. H. (2012). MET signaling regulates glioblastoma stem cells. Cancer Research, 72(15), 3828-3838. https://doi.org/10.1158/0008-5472.CAN-11-3760