PSP94, an upstream signaling mediator of prostasin found highly elevated in ovarian cancer.
PSP94, an upstream signaling mediator of prostasin found highly elevated in ovarian cancer.
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DOI：
10.1038/cddis.2014.374
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发表时间：
2014-09-04
影响因子：
9
通讯作者：
Yu JJ
中科院分区：
文献类型：
--
作者：
Ma JX;Yan BX;Zhang J;Jiang BH;Guo Y;Riedel H;Mueller MD;Remick SC;Yu JJ
卵巢癌是癌症死亡的主要原因，因为诊断经常被延迟到晚期。迫切需要有效的生物标志物和早期检测的筛查策略。在当前的研究中，我们确定 PSP94 是介导前列腺素（一种先前报道在卵巢癌中过度表达的蛋白质）信号传导的关键上游因子，可调节前列腺素在卵巢癌细胞中的表达和作用。 PSP94 在卵巢癌细胞系和患者中过度表达，并且与前列腺素水平显着相关。信号通路分析表明，PSP94 和前列腺素作为 Lin28b/Let-7 通路的潜在上游调节因子，在卵巢癌细胞中调节 Lin28b 及其下游伴侣 Let-7。卵巢癌患者中 PSP94 和前列腺素的表达与 Lin28b/Let-7 的表达水平密切相关。因此，PSP94/前列腺素轴似乎与 Lin28b/Let-7 环有关，Lin28b/Let-7 环是肿瘤发生中众所周知的信号机制，在卵巢癌中也发生了改变。研究结果表明PSP94和PSP94/前列腺素轴是卵巢癌的关键因素和潜在治疗靶点或早期生物标志物。
Ovarian cancer is a leading cause of cancer death as diagnosis is frequently delayed to an advanced stage. Effective biomarkers and screening strategies for early detection are urgently needed. In the current study, we identify PSP94 as a key upstream factor in mediating prostasin (a protein previously reported to be overexpressed in ovarian cancer) signaling that regulates prostasin expression and action in ovarian cancer cells. PSP94 is overexpressed in ovarian cancer cell lines and patients, and is significantly correlated with prostasin levels. Signaling pathway analysis demonstrated that both PSP94 and prostasin, as potential upstream regulators of the Lin28b/Let-7 pathway, regulate Lin28b and its downstream partner Let-7 in ovarian cancer cells. Expression of PSP94 and prostasin show a strong correlation with the expression levels of Lin28b/Let-7 in ovarian cancer patients. Thus, PSP94/prostasin axis appears to be linked to the Lin28b/Let-7 loop, a well-known signaling mechanism in oncogenesis in general that is also altered in ovarian cancer. The findings suggest that PSP94 and PSP94/prostasin axis are key factors and potential therapeutic targets or early biomarkers for ovarian cancer.