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Comment
. 2014 Sep 17;33(18):1984-6.
doi: 10.15252/embj.201489479. Epub 2014 Jul 24.

Sox2, a marker for stem-like tumor cells in skin squamous cell carcinoma and hedgehog subgroup medulloblastoma

Oren J Becher  1 , Eric C Holland  2
Affiliations
Comment

Sox2, a marker for stem-like tumor cells in skin squamous cell carcinoma and hedgehog subgroup medulloblastoma

Oren J Becher et al. EMBO J. .

Abstract

Heterogeneity within tumors is becoming increasingly recognized as an important cause of treatment failure in cancer. Two recent studies use fate-mapping and limiting dilution transplantation assays to identify SRY (sex determining region Y)-box 2 (Sox2) as cancer stem-cell marker and driver of cancer stemness.

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Figures

Figure 1
Figure 1. Tumor Hierarchy in Sonic Hedgehog Subgroup MB and skin SCC
(A) In a murine model of sonic hedgehog subgroup medulloblastoma, rare, relatively quiescent Sox2+ cancer stem cells give rise to rapidly proliferating doublecortin+ progenitor cells, which subsequently give rise to postmitotic NeuN+ cells. Whether this hierarchy is reversible, that is, whether a DCX+ cell can become a Sox2+ cell, or whether a NeuN+ cell can revert to a DCX+ cell remains to be elucidated. (B) In a murine model of skin squamous cell carcinoma, rapidly proliferating Sox2+ cells, which account for 25% of the total tumor population, give rise to Sox2− cells. This differentiation step appears inefficiently reversible. Furthermore, Sox2 is not only a cancer stem cell marker but also a driver of stemness in this tumor type.
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Comment on

  • Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.
    Kool M, Jones DT, Jäger N, Northcott PA, Pugh TJ, Hovestadt V, Piro RM, Esparza LA, Markant SL, Remke M, Milde T, Bourdeaut F, Ryzhova M, Sturm D, Pfaff E, Stark S, Hutter S, Seker-Cin H, Johann P, Bender S, Schmidt C, Rausch T, Shih D, Reimand J, Sieber L, Wittmann A, Linke L, Witt H, Weber UD, Zapatka M, König R, Beroukhim R, Bergthold G, van Sluis P, Volckmann R, Koster J, Versteeg R, Schmidt S, Wolf S, Lawerenz C, Bartholomae CC, von Kalle C, Unterberg A, Herold-Mende C, Hofer S, Kulozik AE, von Deimling A, Scheurlen W, Felsberg J, Reifenberger G, Hasselblatt M, Crawford JR, Grant GA, Jabado N, Perry A, Cowdrey C, Croul S, Zadeh G, Korbel JO, Doz F, Delattre O, Bader GD, McCabe MG, Collins VP, Kieran MW, Cho YJ, Pomeroy SL, Witt O, Brors B, Taylor MD, Schüller U, Korshunov A, Eils R, Wechsler-Reya RJ, Lichter P, Pfister SM; ICGC PedBrain Tumor Project. Kool M, et al. Cancer Cell. 2014 Mar 17;25(3):393-405. doi: 10.1016/j.ccr.2014.02.004. Cancer Cell. 2014. PMID: 24651015 Free PMC article.
  • SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma.
    Boumahdi S, Driessens G, Lapouge G, Rorive S, Nassar D, Le Mercier M, Delatte B, Caauwe A, Lenglez S, Nkusi E, Brohée S, Salmon I, Dubois C, del Marmol V, Fuks F, Beck B, Blanpain C. Boumahdi S, et al. Nature. 2014 Jul 10;511(7508):246-50. doi: 10.1038/nature13305. Epub 2014 Jun 8. Nature. 2014. PMID: 24909994
  • Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma.
    Vanner RJ, Remke M, Gallo M, Selvadurai HJ, Coutinho F, Lee L, Kushida M, Head R, Morrissy S, Zhu X, Aviv T, Voisin V, Clarke ID, Li Y, Mungall AJ, Moore RA, Ma Y, Jones SJ, Marra MA, Malkin D, Northcott PA, Kool M, Pfister SM, Bader G, Hochedlinger K, Korshunov A, Taylor MD, Dirks PB. Vanner RJ, et al. Cancer Cell. 2014 Jul 14;26(1):33-47. doi: 10.1016/j.ccr.2014.05.005. Epub 2014 Jun 19. Cancer Cell. 2014. PMID: 24954133 Free PMC article.

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