SOX5/6/21 prevent oncogene-driven transformation of brain stem cells

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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SOX5/6/21 prevent oncogene-driven transformation of brain stem cells. / Kurtsdotter, Idha; Topcic, Danijal; Karlén, Alexandra; Singla, Bhumica; Hagey, Daniel W.; Bergsland, Maria; Siesjö, Peter; Nistér, Monica; Carlson, Joseph W.; Lefebvre, Veronique; Persson, Oscar; Holmberg, Johan; Muhr, Jonas.

I: Cancer Research, Vol. 77, Nr. 18, 15.09.2017, s. 4985-4997.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Kurtsdotter, I, Topcic, D, Karlén, A, Singla, B, Hagey, DW, Bergsland, M, Siesjö, P, Nistér, M, Carlson, JW, Lefebvre, V, Persson, O, Holmberg, J & Muhr, J 2017, 'SOX5/6/21 prevent oncogene-driven transformation of brain stem cells', Cancer Research, vol. 77, nr. 18, s. 4985-4997. https://doi.org/10.1158/0008-5472.CAN-17-0704

APA

Kurtsdotter, I., Topcic, D., Karlén, A., Singla, B., Hagey, D. W., Bergsland, M., ... Muhr, J. (2017). SOX5/6/21 prevent oncogene-driven transformation of brain stem cells. Cancer Research, 77(18), 4985-4997. https://doi.org/10.1158/0008-5472.CAN-17-0704

CBE

Kurtsdotter I, Topcic D, Karlén A, Singla B, Hagey DW, Bergsland M, Siesjö P, Nistér M, Carlson JW, Lefebvre V, Persson O, Holmberg J, Muhr J. 2017. SOX5/6/21 prevent oncogene-driven transformation of brain stem cells. Cancer Research. 77(18):4985-4997. https://doi.org/10.1158/0008-5472.CAN-17-0704

MLA

Vancouver

Kurtsdotter I, Topcic D, Karlén A, Singla B, Hagey DW, Bergsland M et al. SOX5/6/21 prevent oncogene-driven transformation of brain stem cells. Cancer Research. 2017 sep 15;77(18):4985-4997. https://doi.org/10.1158/0008-5472.CAN-17-0704

Author

Kurtsdotter, Idha ; Topcic, Danijal ; Karlén, Alexandra ; Singla, Bhumica ; Hagey, Daniel W. ; Bergsland, Maria ; Siesjö, Peter ; Nistér, Monica ; Carlson, Joseph W. ; Lefebvre, Veronique ; Persson, Oscar ; Holmberg, Johan ; Muhr, Jonas. / SOX5/6/21 prevent oncogene-driven transformation of brain stem cells. I: Cancer Research. 2017 ; Vol. 77, Nr. 18. s. 4985-4997.

RIS

TY - JOUR

T1 - SOX5/6/21 prevent oncogene-driven transformation of brain stem cells

AU - Kurtsdotter, Idha

AU - Topcic, Danijal

AU - Karlén, Alexandra

AU - Singla, Bhumica

AU - Hagey, Daniel W.

AU - Bergsland, Maria

AU - Siesjö, Peter

AU - Nistér, Monica

AU - Carlson, Joseph W.

AU - Lefebvre, Veronique

AU - Persson, Oscar

AU - Holmberg, Johan

AU - Muhr, Jonas

PY - 2017/9/15

Y1 - 2017/9/15

N2 - Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model. Loss-of-function experiments revealed that SOX5/6/21 prevent detrimental hyperproliferation of oncogene expressing SVZ cells by facilitating an antiproliferative expression profile. Consistently, restoring high levels of SOX5/6/21 in human primary glioblastoma cells enabled expression of CDK inhibitors and decreased p53 protein turnover, which blocked their tumorigenic capacity through cellular senescence and apoptosis. Altogether, these results provide evidence that SOX5/6/21 play a central role in driving a tumor suppressor response in brain stem cells upon oncogenic insult.

AB - Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model. Loss-of-function experiments revealed that SOX5/6/21 prevent detrimental hyperproliferation of oncogene expressing SVZ cells by facilitating an antiproliferative expression profile. Consistently, restoring high levels of SOX5/6/21 in human primary glioblastoma cells enabled expression of CDK inhibitors and decreased p53 protein turnover, which blocked their tumorigenic capacity through cellular senescence and apoptosis. Altogether, these results provide evidence that SOX5/6/21 play a central role in driving a tumor suppressor response in brain stem cells upon oncogenic insult.

UR - http://www.scopus.com/inward/record.url?scp=85031404985&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-17-0704

DO - 10.1158/0008-5472.CAN-17-0704

M3 - Article

VL - 77

SP - 4985

EP - 4997

JO - Cancer research. Supplement

T2 - Cancer research. Supplement

JF - Cancer research. Supplement

SN - 1538-7445

IS - 18

ER -