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首页> 外文期刊>Neoplasia: an international journal for oncology research >AMOTL1 Promotes Breast Cancer Progression and Is Antagonized by Merlin
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AMOTL1 Promotes Breast Cancer Progression and Is Antagonized by Merlin

机译：amoTl1促进乳腺癌进展，并由Merlin拮抗

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The Hippo signaling network is a key regulator of cell fate. In the recent years, it was shown that its implication in cancer goes well beyond the sole role of YAP transcriptional activity and its regulation by the canonical MST/LATS kinase cascade. Here we show that the motin family member AMOTL1 is an important effector of Hippo signaling in breast cancer. AMOTL1 connects Hippo signaling to tumor cell aggressiveness. We show that both canonical and noncanonical Hippo signaling modulates AMOTL1 levels. The tumor suppressor Merlin triggers AMOTL1 proteasomal degradation mediated by the NEDD family of ubiquitin ligases through direct interaction. In parallel, YAP stimulates AMOTL1 expression. The loss of Merlin expression and the induction of Yap activity that are frequently observed in breast cancers thus result in elevated AMOTL1 levels. AMOTL1 expression is sufficient to trigger tumor cell migration and stimulates proliferation by activating c-Src. In a large cohort of human breast tumors, we show that AMOTL1 protein levels are upregulated during cancer progression and that, importantly, the expression of AMOTL1 in lymph node metastasis appears predictive of the risk of relapse. Hence we uncover an important mechanism by which Hippo signaling promotes breast cancer progression by modulating the expression of AMOTL1.
机译：河马信令网络是单元命运的关键稳压器。近年来，表明其在癌症中的含义远远超出了Yap转录活性及其通过规范MST / LAT激酶级联的唯一作用。在这里，我们显示Motin家族成员AmoT11是乳腺癌中河马信号传导的重要效应。 amoTl1将河马信号通信到肿瘤细胞侵略性。我们展示了规范和非甘露狼人的河马信号传导调制amotl1水平。通过直接相互作用，肿瘤抑制剂Merlin触发由NEDDD系列泛素连接酶介导的NEDD系列介导的amotl1蛋白酶体降解。平行，yap刺激amotl1表达。因此，在乳腺癌中经常观察到的Merlin表达和诱导乳房活性的诱导导致AMOTL1水平升高。 AMOTL1表达足以通过激活C-SRC来引发肿瘤细胞迁移并刺激增殖。在大量的人类乳腺肿瘤中，我们表明，在癌症进展期间上调AMOT11蛋白水平，结果，重要的是，淋巴结转移中的AMOTL1的表达似乎预测了复发风险的预测。因此，我们发现河马信号传导通过调节AmOTL1的表达来促进乳腺癌进展的重要机制。

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