Mesenchymal transdifferentiation in brain cancer stem cells:
One of my recent scientific achievements is the discovery of two mutually-exclusive subtypes of cancer stem cells with clinical relevance. In particular, one of these subtypes, Mes CSCs are more aggressive and therapy resistant. Some of our recent papers have elucidated the molecular mechanisms for therapy resistance in Mes CSCs.
a. Mesenchymal Glioma Stem Cells are Maintained by Activated Glycolytic Metabolism Involving Aldehyde Dehydrogenase 1A3. Mao P, Kim SH, Li J, Joshi K, Li PP, Santana-Santos L, Luthra S, Chandran UR, Benos PV, Smith L, Wang MD, Hu B, Cheng SY, Sobol RW, Nakano I. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8644-9. PMID: 23650391 *selected as Research Highlights by the Association of American Cancer Institutes, and selected by the ASCO POST
b. Mesenchymal Differentiation Mediated by NFB Promotes Radiation Resistance in Glioblastoma. Bhat KPL, Balasubramaniyan V, Vaillant B, Ezhilarasan R, Hummelink K, Hollingsworth F, Wani K, Heathcock L, James JD, Goodman LD, Conroy S, Long L, Lelic N, Wang S, Gumin J, Raj D, Kodama Y, Raghunathan A, Olar A, Joshi K, Pelloski CE, Heimberger A, Kim SH, Cahill DP, Rao G, denDunnen WFA, Boddeke HWGM, Phillips HS, Nakano I, Lang FF, Colman H, Sulman EP, and Aldape K. Cancer Cell 2013 Sep 9;24(3):331-46. doi: 10.1016/j.ccr.2013.08.001. *Editor’s Choice in Sci. Signal., 17 September 2013 Vol. 6, Issue 293, p. ec223 DOI: 10.1126/scisignal.2004728
c. Proneural-mesenchymal transformation of glioma stem cells: do therapies cause evolution of target in glioblastoma? Nakano I. Future Oncol. 2014;10(9):1527-30. doi: 10.2217/fon.14.86.
d. Kinome-wide shRNA Screen Identifies the Receptor Tyrosine Kinase AXL as a Key Regulator for Mesenchymal Glioblastoma Stem-Like Cells. Cheng P, Phillips E, Kim SH, Taylor D, Hielscher T, Puccio L, Hjelmeland A, Lichter P, Nakano I* (co-corresponding author), Goidts V*. Stem Cell Reports 2015 [in press]