来自美国得克萨斯大学西南医学中心等处的研究人员证明了一种PI3K/PTEN调控环路中的新成分，并提出这种成分可以作为一种抗肿瘤的新靶标。
PTEN是一种重要的具有磷酸酶活性的信号因子，PI3K/PTEN信号通路作用广泛，能调节一系列基本的细胞反应。PTEN基因可通过基因突变、DNA甲基化等方式失活，主要表现为基因缺失、蛋白表达减少。PTEN作用于PI3K／AKT信号途径和选择性抑制MAPK途径，调控细胞增殖；通过发挥蛋白磷酸酶功能，使FAK和SHC去磷酸化，抑制细胞迁移。PTEN在卵巢癌的发生、发展中发挥着重要作用。
在这篇文章中，研究人员发现了一种内质网酶：ENTPD5在原代人类肿瘤样品，以及细胞系中，伴随着AKT的增长而增加研究人员通过一系列实验证明ENTPD5是PI3K/PTEN作用途径中的一部分，因此能作为一种潜在的抗肿瘤治疗靶标。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
