Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression

Xun Jin; Xiong Jin; Young Woo Sohn; Jinlong Yin; Sung Hak Kim; Kaushal Joshi; Do Hyun Nam; Ichiro Nakano; Hyunggee Kim

doi:10.1016/j.canlet.2012.09.005

Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27^KIP1 and MMP3 expression

Xun Jin
, Xiong Jin
, Young Woo Sohn
, Jinlong Yin
, Sung Hak Kim
, Kaushal Joshi
, Do Hyun Nam
, Ichiro Nakano
, Hyunggee Kim^*

^*Corresponding author for this work

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

33 Citations (Scopus)

Abstract

Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27^KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27^KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27^KIP1 and MMP3 expression.

Original language	English
Pages (from-to)	235-242
Number of pages	8
Journal	Cancer letters
Volume	328
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2012.09.005
Publication status	Published - 2013 Jan 28

Bibliographical note

Funding Information:
This work was supported by the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1020270), the American Cancer Society (MRSG-08-108-01) and NIH/NCI (1R21CA135013-01A1). X.J. and S.H.K. were supported by a postdoctoral fellowship program from the Brain Korea 21 project funded by MEST. X.J. and Y.W.S. were supported by a graduate fellowship program from the Brain Korea 21 project funded by MEST. We thank Dr. Akio Soeda for providing X01, X02, and X03 GSCs.

Keywords

EGFR
Glioblastoma
Glioma stem cells
ID3
Invasion

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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

Access to Document

10.1016/j.canlet.2012.09.005

Cite this

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title = "Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression",

abstract = "Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression.",

keywords = "EGFR, Glioblastoma, Glioma stem cells, ID3, Invasion",

author = "Xun Jin and Xiong Jin and Sohn, \{Young Woo\} and Jinlong Yin and Kim, \{Sung Hak\} and Kaushal Joshi and Nam, \{Do Hyun\} and Ichiro Nakano and Hyunggee Kim",

note = "Funding Information: This work was supported by the National R\&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1020270), the American Cancer Society (MRSG-08-108-01) and NIH/NCI (1R21CA135013-01A1). X.J. and S.H.K. were supported by a postdoctoral fellowship program from the Brain Korea 21 project funded by MEST. X.J. and Y.W.S. were supported by a graduate fellowship program from the Brain Korea 21 project funded by MEST. We thank Dr. Akio Soeda for providing X01, X02, and X03 GSCs. ",

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AU - Jin, Xun

AU - Jin, Xiong

AU - Sohn, Young Woo

AU - Yin, Jinlong

AU - Kim, Sung Hak

AU - Joshi, Kaushal

AU - Nam, Do Hyun

AU - Nakano, Ichiro

AU - Kim, Hyunggee

N1 - Funding Information: This work was supported by the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1020270), the American Cancer Society (MRSG-08-108-01) and NIH/NCI (1R21CA135013-01A1). X.J. and S.H.K. were supported by a postdoctoral fellowship program from the Brain Korea 21 project funded by MEST. X.J. and Y.W.S. were supported by a graduate fellowship program from the Brain Korea 21 project funded by MEST. We thank Dr. Akio Soeda for providing X01, X02, and X03 GSCs.

PY - 2013/1/28

Y1 - 2013/1/28

N2 - Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression.

AB - Aberrant epidermal growth factor receptor (EGFR) signaling is a typical oncogenic signature in glioblastoma. Here, we show that EGFR inhibition in primary glioma stem cells (GSCs) with oncogenic EGFRvIII and EGFRvIII-transduced glioma stem-like cells promotes invasion by decreasing ID3 levels. ID3 suppresses GSC invasiveness by inhibiting p27KIP1-RhoA-dependent migration and MMP3 expression. Xenograft and human glioblastoma specimens show that ID3 localizes within glioblastoma cores, whereas p27KIP1 and MMP3 are predominantly expressed in glioma cells in invasive fronts. Together, our findings show that EGFR inhibition induces GSC invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression.

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KW - Glioblastoma

KW - Glioma stem cells

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