Phosphatidylinositol 3-kinase, class 2 beta (PI3KC2β) isoform contributes to neuroblastoma tumorigenesis.
Phosphatidylinositol 3-kinase, class 2 beta (PI3KC2β) isoform contributes to neuroblastoma tumorigenesis.
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DOI：
10.1016/j.canlet.2015.01.026
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发表时间：
2015-04-10
期刊：
影响因子：
9.7
通讯作者：
O'Bryan, John P.
中科院分区：
文献类型：
--
作者：
Russo, Angela;Okur, Mustafa Nazir;Bosland, Maarten;O'Bryan, John P.
磷脂酰肌醇3-激酶（pi3k）在人类肿瘤发生中起重要作用。PI3K靶AKT的激活在神经母细胞瘤（NB）中很常见，并与不良预后相关。PI3K泛抑制剂可以减少NB肿瘤的形成，但存在严重的毒性，这限制了它们的治疗潜力。因此，确定特定PI3K亚型的重要性可能有助于开发更有效的治疗策略。我们之前已经证明PI3K类IIβ (PI3KC2β)及其调节因子交叉蛋白1 （ITSN1）在原发性NB肿瘤和细胞系中高表达。沉默ITSN1显著降低NB细胞的致瘤潜能。有趣的是，PI3KC2β的过表达挽救了ITSN1沉默细胞的锚定非依赖性生长，这表明PI3KC2β介导了ITSN1在NB细胞中的功能。为了说明PI3KC2β在NBs中的重要性，我们生成了PI3KC2β沉默系并检测了它们的生物活性。在此，我们证明pi3kc2 β-沉默抑制NB早期致瘤性生长。我们还发现，内源性PI3KC2β或ITSN1的缺失会降低AKT的激活，但不会影响ERK-MAPK的激活。这些数据揭示了PI3KC2β在人NB肿瘤发生中的新作用。
Phosphatidylinositol 3-kinases (PI3Ks) play important roles in human tumorigenesis. Activation of the PI3K target AKT is frequent in neuroblastoma (NB) and correlates with poor prognosis. PI3K pan-inhibitors reduce NB tumor formation but present severe toxicity, which limits their therapeutic potential. Therefore, defining the importance of specific PI3K isoforms may aid in developing more effective therapeutic strategies. We previously demonstrated that PI3K Class IIβ (PI3KC2β) and its regulator intersectin 1 (ITSN1) are highly expressed in primary NB tumors and cell lines. Silencing ITSN1 dramatically reduced the tumorigenic potential of NB cells. Interestingly, overexpression of PI3KC2β rescued the anchorage-independent growth of ITSN1-silenced cells suggesting that PI3KC2β mediates ITSN1's function in NB cells. To address the importance of PI3KC2β in NBs, we generated PI3KC2β-silenced lines and examined their biologic activity. Herein, we demonstrate that PI3KC2β-silencing inhibits early stages of NB tumorigenic growth. We also show that loss of endogenous PI3KC2β or ITSN1 reduces AKT activation but does not impact ERK-MAPK activation. These data reveal a novel role for PI3KC2β in human NB tumorigenesis.
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影响因子：
30.8
作者：
Armstrong, SA;Staunton, JE;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
8
作者：
Billottet, C.;Grandage, V. L.;Khwaja, A.
通讯作者：
Khwaja, A.
影响因子：
3.3
作者：
Srivastava, Shekhar;Di, Lie;Skolnik, Edward Y.
通讯作者：
Skolnik, Edward Y.
DOI：
10.1016/j.bbapap.2007.10.003
发表时间：
2008-01-01
影响因子：
3.2
作者：
Marone, Romina;Cmijanovic, Vladimir;Wymann, Matthias P.
通讯作者：
Wymann, Matthias P.
影响因子：
4.1
作者：
Crljen, V;Volinia, S;Banfic, H
通讯作者：
Banfic, H