Chang Yung-Sheng, Chen Wei-Yu, Yin Juan Juan, Sheppard-Tillman Heather, Huang Jiaoti, Liu Yen-Nien
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Cancer Res. 2015 Aug 1;75(15):3077-86. doi: 10.1158/0008-5472.CAN-14-3380. Epub 2015 Jun 12.
Dysregulation of the EGFR signaling axis enhances bone metastases in many solid cancers. However, the relevant downstream effector signals in this axis are unclear. miR-1 was recently shown to function as a tumor suppressor in prostate cancer cells, where its expression correlated with reduced metastatic potential. In this study, we demonstrated a role for EGFR translocation in regulating transcription of miR-1-1, which directly targets expression of TWIST1. Consistent with these findings, we observed decreased miR-1 levels that correlated with enhanced expression of activated EGFR and TWIST1 in a cohort of human prostate cancer specimens and additional datasets. Our findings support a model in which nuclear EGFR acts as a transcriptional repressor to constrain the tumor-suppressive role of miR-1 and sustain oncogenic activation of TWIST1, thereby leading to accelerated bone metastasis.
表皮生长因子受体（EGFR）信号轴的失调在许多实体癌中会增强骨转移。然而，该信号轴中相关的下游效应信号尚不清楚。最近研究表明，miR-1在前列腺癌细胞中发挥肿瘤抑制作用，其表达与转移潜能降低相关。在本研究中，我们证明了EGFR易位在调节miR-1-1转录中的作用，miR-1-1直接靶向TWIST1的表达。与这些发现一致，我们在一组人类前列腺癌标本和其他数据集中观察到miR-1水平降低，这与活化的EGFR和TWIST1表达增强相关。我们的研究结果支持一种模型，即核内EGFR作为转录抑制因子，限制miR-1的肿瘤抑制作用并维持TWIST1的致癌激活，从而导致骨转移加速。
