A vicious partnership between AKT and PHLDA3 to facilitate neuroendocrine tumors.
A vicious partnership between AKT and PHLDA3 to facilitate neuroendocrine tumors.
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DOI：
10.1111/cas.13235
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发表时间：
2017-06
期刊：
影响因子：
5.7
通讯作者：
Ohki R
中科院分区：
文献类型：
--
作者：
Takikawa M;Ohki R
胰腺神经内分泌肿瘤（PanNET）是一种罕见的癌症，通常预后不良。这些肿瘤的准确诊断和适当治疗需要更好地了解PanNET发展的分子机制。研究表明，mTOR抑制剂依维莫司可以改善PanNET患者的无进展生存期，这表明抑制PI 3 K-Akt-mTOR通路可能会抑制PanNET的进展。PHLDA 3是一种新型的肿瘤抑制蛋白，其通过竞争结合PIP 3来抑制Akt活化。我们对PanNET的分析揭示了PHLDA 3基因座频繁的杂合性缺失和DNA甲基化，导致了对PHLDA 3转录的强烈抑制。PHLDA 3基因的这种改变也经常在肺神经内分泌肿瘤（NET）中发现，这表明各种类型的NET可能共同具有PHLDA 3基因的功能丧失。
Pancreatic neuroendocrine tumors (PanNET) are rare cancers that generally have a poor prognosis. Accurate diagnosis and proper treatment of these tumors requires a better understanding of the molecular mechanisms underlying the development of PanNET. It has been shown that the mTOR inhibitor everolimus can improve the progression‐free survival of PanNET patients, suggesting that inhibition of the PI3K‐Akt‐mTOR pathway may suppress the progression of PanNET. PHLDA3 is a novel tumor suppressor protein that inhibits Akt activation by competition for binding to PIP 3. Our analysis of PanNET revealed frequent loss‐of‐heterozygosity and DNA methylation at the PHLDA3 locus, resulting in strong suppression of PHLDA3 transcription. Such alterations in the PHLDA3 gene were also frequently found in lung neuroendocrine tumors (NET), suggesting the possibility that various types of NET have in common the functional loss of the PHLDA3 gene.