Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

Hye Min Jeon; Xun Jin; Joong Seob Lee; Se Yeong Oh; Young Woo Sohn; Hyo Jung Park; Min Joo Kyeung; Woong Yang Park; Do Hyun Nam; Ronald A. DePinho; Lynda Chin; Hyunggee Kim

doi:10.1101/gad.1668708

Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

Hye Min Jeon, Xun Jin, Joong Seob Lee, Se Yeong Oh, Young Woo Sohn, Hyo Jung Park, Min Joo Kyeung, Woong Yang Park, Do Hyun Nam, Ronald A. DePinho, Lynda Chin, Hyunggee Kim

Research output: Contribution to journal › Article › peer-review

106 Citations (Scopus)

Abstract

Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf^-/- astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.

Original language	English
Pages (from-to)	2028-2033
Number of pages	6
Journal	Genes and Development
Volume	22
Issue number	15
DOIs	https://doi.org/10.1101/gad.1668708
Publication status	Published - 2008 Aug 1

Keywords

Cyclin E
Glioblastoma
Id4
Ink4a/Arf astrocyte
Neural stem-like cells
Notch signaling

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.1668708

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title = "Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling",

abstract = "Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf-/- astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.",

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doi = "10.1101/gad.1668708",

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AU - Jeon, Hye Min

AU - Jin, Xun

AU - Lee, Joong Seob

AU - Oh, Se Yeong

AU - Sohn, Young Woo

AU - Park, Hyo Jung

AU - Kyeung, Min Joo

AU - Park, Woong Yang

AU - Nam, Do Hyun

AU - DePinho, Ronald A.

AU - Chin, Lynda

AU - Kim, Hyunggee

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf-/- astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.

AB - Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf-/- astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.

KW - Cyclin E

KW - Glioblastoma

KW - Id4

KW - Ink4a/Arf astrocyte

KW - Neural stem-like cells

KW - Notch signaling

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Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

Abstract

Keywords

ASJC Scopus subject areas

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