Fang 2010 Cell

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Publications in the MiPMap
Fang M, Shen Z, Huang S, Zhao L, Chen S, Mak TW, Wang X (2010) The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway. Cell 143:711-24.

» PMID: 21074248; sciencedirect Open Access

Fang M, Shen Z, Huang S, Zhao L, Chen S, Mak TW, Wang X (2010) Cell

Abstract: PI3K and PTEN lipid phosphatase control the level of cellular phosphatidylinositol (3,4,5)-trisphosphate, an activator of AKT kinases that promotes cell growth and survival. Mutations activating AKT are commonly observed in human cancers. We report here that ENTPD5, an endoplasmic reticulum (ER) enzyme, is upregulated in cell lines and primary human tumor samples with active AKT. ENTPD5 hydrolyzes UDP to UMP to promote protein N-glycosylation and folding in ER. Knockdown of ENTPD5 in PTEN null cells causes ER stress and loss of growth factor receptors. ENTPD5, together with cytidine monophosphate kinase-1 and adenylate kinase-1, constitute an ATP hydrolysis cycle that converts ATP to AMP, resulting in a compensatory increase in aerobic glycolysis known as the Warburg effect. The growth of PTEN null cells is inhibited both in vitro and in mouse xenograft tumor models. ENTPD5 is therefore an integral part of the PI3K/PTEN regulatory loop and a potential target for anticancer therapy

Keywords: Warburg effect

O2k-Network Lab: US TX Dallas Wang X, CN Beijing Wang X


Labels: MiParea: Respiration  Pathology: Cancer 


Preparation: Intact cells 

Regulation: Aerobic glycolysis  Coupling state: OXPHOS 

HRR: Oxygraph-2k 


Oxygraph-2k application

In this publication and in Supplemental Information (EXTENDED EXPERIMENTAL PROCEDURES) respirometric results on intact cells are described which are based on applications of the Oroboros Oxygraph-2k (Dr. Huang Song, personal communication).

The Warburg effect