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The Anti-Warburg Effect Elicited by the cAMP-PGC1α Pathway Drives Differentiation of Glioblastoma Cells into Astrocytes.

Abstract：

:Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM. Dibutyryl cyclic AMP (dbcAMP) reverses the Warburg effect, as evidenced by increased oxygen consumption and reduced lactate production. Mitochondrial biogenesis induced by activation of the CREB-PGC1α pathway triggers metabolic shift and differentiation. Blocking mitochondrial biogenesis using mdivi1 or by silencing PGC1α abrogates differentiation; conversely, overexpression of PGC1α elicits differentiation. In GBM xenograft models and patient-derived GBM samples, cAMP activators also induce tumor growth inhibition and differentiation. Our data show that mitochondrial biogenesis and metabolic switch to oxidative phosphorylation drive the differentiation of tumor cells.

journal_name

Cell Rep

journal_title

Cell reports

authors

Xing F,Luan Y,Cai J,Wu S,Mai J,Gu J,Zhang H,Li K,Lin Y,Xiao X,Liang J,Li Y,Chen W,Tan Y,Sheng L,Lu B,Lu W,Gao M,Qiu P,Su X,Yin W,Hu J,Chen Z,Sai K,Wang J,Chen F,Chen Y,Zhu S,Liu D,Cheng S,Xie Z

doi

10.1016/j.celrep.2016.12.037

subject

Has Abstract

pub_date

2017-01-10 00:00:00

pages

468-481

issue

2

issn

2211-1247

pii

S2211-1247(16)31742-9

journal_volume

18

pub_type

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