來(lái)自美國(guó)得克薩斯大學(xué)西南醫(yī)學(xué)中心等處的研究人員證明了一種PI3K/PTEN調(diào)控環(huán)路中的新成分,，并提出這種成分可以作為一種抗腫瘤的新靶標(biāo),。
PTEN是一種重要的具有磷酸酶活性的信號(hào)因子，PI3K/PTEN信號(hào)通路作用廣泛,，能調(diào)節(jié)一系列基本的細(xì)胞反應(yīng),。PTEN基因可通過(guò)基因突變、DNA甲基化等方式失活,，主要表現(xiàn)為基因缺失,、蛋白表達(dá)減少,。PTEN作用于PI3K／AKT信號(hào)途徑和選擇性抑制MAPK途徑,，調(diào)控細(xì)胞增殖,；通過(guò)發(fā)揮蛋白磷酸酶功能，使FAK和SHC去磷酸化,，抑制細(xì)胞遷移,。PTEN在卵巢癌的發(fā)生、發(fā)展中發(fā)揮著重要作用,。
在這篇文章中,，研究人員發(fā)現(xiàn)了一種內(nèi)質(zhì)網(wǎng)酶：ENTPD5在原代人類(lèi)腫瘤樣品，以及細(xì)胞系中,，伴隨著AKT的增長(zhǎng)而增加研究人員通過(guò)一系列實(shí)驗(yàn)證明ENTPD5是PI3K/PTEN作用途徑中的一部分,，因此能作為一種潛在的抗腫瘤治療靶標(biāo)。（生物谷Bioon.com）
生物谷推薦原文出處：
Cell doi:10.1016/j.cell.2010.10.010
The ER UDPase ENTPD5 Promotes Protein N-Glycosylation, the Warburg Effect, and Proliferation in the PTEN Pathway
Highlights
The ER UDPase ENTPD5 is upregulated by AKT in PTEN mutant cells
ENTPD5 hydrolyzes UDP to UMP to promote protein N-glycosylation
ENTPD5, along with CMPK1 and AK-1, hydrolyze ATP to AMP, increasing aerobic glycolysis
ENTPD5 knockdown attenuates growth factor expression and tumor growth
Summary
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.
