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

Department of Neurosurgery

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

109 Scopus citations

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
State	Published - 1 Aug 2008

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1101/gad.1668708

Cite this

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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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year = "2008",

month = aug,

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doi = "10.1101/gad.1668708",

language = "English",

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journal = "Genes and Development",

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publisher = "Cold Spring Harbor Laboratory Press",

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TY - JOUR

T1 - Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

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

UR - https://www.scopus.com/pages/publications/48749083583

U2 - 10.1101/gad.1668708

DO - 10.1101/gad.1668708

M3 - Article

C2 - 18676808

AN - SCOPUS:48749083583

SN - 0890-9369

VL - 22

SP - 2028

EP - 2033

JO - Genes and Development

JF - Genes and Development

IS - 15

ER -

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

Abstract

Keywords

UN SDGs

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