INPP4B is an oncogenic regulator in human colon cancer.
INPP4B is an oncogenic regulator in human colon cancer.
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INPP4B 是人类结肠癌的致癌调节因子。
DOI：
10.1038/onc.2015.361
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发表时间：
2016-06-09
期刊：
影响因子：
8
通讯作者：
Jiang CC
中科院分区：
文献类型：
--
作者：
Guo ST;Chi MN;Yang RH;Guo XY;Zan LK;Wang CY;Xi YF;Jin L;Croft A;Tseng HY;Yan XG;Farrelly M;Wang FH;Lai F;Wang JF;Li YP;Ackland S;Scott R;Agoulnik IU;Hondermarck H;Thorne RF;Liu T;Zhang XD;Jiang CC
肌醇多磷酸4-磷酸酶II型（INPP 4 B）负调节磷脂酰肌醇3-激酶信号传导，是某些类型癌症的肿瘤抑制因子。然而，我们发现它在人结肠癌细胞中经常上调。在这里，我们表明，沉默INPP 4 B阻断Akt和血清和糖皮质激素调节激酶3（SGK 3）的激活，抑制结肠癌细胞增殖，并延缓结肠癌异种移植物的生长。相反，INPP 4 B的过表达增加增殖并触发正常结肠上皮细胞的锚定非依赖性生长。此外，我们证明了INPP 4 B对Akt和SGK 3的作用与磷酸盐和张力蛋白同系物通过其蛋白磷酸酶活性的失活有关，并且INPP 4 B的增加是由于Ets-1介导的结肠癌细胞转录上调。总的来说，这些结果表明，INPP 4 B可能在结肠癌中起致癌驱动作用，具有靶向INPP 4 B作为治疗这种疾病的新方法的潜在意义。
Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum- and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease.