TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma.

Abstract:

:Glioma-initiating cells (GICs) are responsible for the initiation and recurrence of gliomas. Here, we identify a molecular mechanism that regulates the self-renewal capacity of patient-derived GICs. We show that TGF-beta and LIF induce the self-renewal capacity and prevent the differentiation of GICs. TGF-beta induces the self-renewal capacity of GICs, but not of normal human neuroprogenitors, through the Smad-dependent induction of LIF and the subsequent activation of the JAK-STAT pathway. The effect of TGF-beta and LIF on GICs promotes oncogenesis in vivo. Some human gliomas express high levels of LIF that correlate with high expression of TGF-beta2 and neuroprogenitor cell markers. Our results show that TGF-beta and LIF have an essential role in the regulation of GICs in human glioblastoma.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Peñuelas S,Anido J,Prieto-Sánchez RM,Folch G,Barba I,Cuartas I,García-Dorado D,Poca MA,Sahuquillo J,Baselga J,Seoane J

doi

10.1016/j.ccr.2009.02.011

subject

Has Abstract

pub_date

2009-04-07 00:00:00

pages

315-27

issue

4

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(09)00042-7

journal_volume

15

pub_type

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