TAp63 suppresses mammary tumorigenesis through regulation of the Hippo pathway.
TAp63 suppresses mammary tumorigenesis through regulation of the Hippo pathway.
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DOI：
10.1038/onc.2016.388
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发表时间：
2017-04-27
期刊：
影响因子：
8
通讯作者：
Flores ER
中科院分区：
文献类型：
--
作者：
Su X;Napoli M;Abbas HA;Venkatanarayan A;Bui NHB;Coarfa C;Gi YJ;Kittrell F;Gunaratne PH;Medina D;Rosen JM;Behbod F;Flores ER
乳腺上皮细胞(MECs)向乳腺干细胞(MASCs)和肿瘤起始细胞(TICs)转化的调控机制尚未完全阐明。P53家族成员p63对乳腺发育至关重要，包含具有抑癌活性的反式激活域异构体和癌基因ΔN异构体。在临床上，P63经常被用作诊断标记物，进一步分析TAp63在乳腺中的功能对于提高诊断和患者护理至关重要。TAp63基因缺失会导致小鼠在9-16个月龄时形成侵袭性转移性乳腺癌。在这里，我们表明TAp63在乳腺癌细胞向抽动的转变过程中是至关重要的。当TAp63丢失时，MEC表达胚胎和MASC信号，并激活河马途径。这些数据表明TAp63在乳腺学中起着至关重要的作用，并为其在乳腺癌中作为肿瘤和转移抑制因子的作用提供了机制。
Mechanisms regulating the transition of mammary epithelial cells (MECs) to mammary stem cells (MaSCs) and to tumor-initiating cells (TICs) have not been entirely elucidated. The p53 family member, p63, is critical for mammary gland development and contains transactivation domain isoforms, which have tumor-suppressive activities, and the ΔN isoforms, which act as oncogenes. In the clinic, p63 is often used as a diagnostic marker, and further analysis of the function of TAp63 in the mammary gland is critical for improved diagnosis and patient care. Loss of TAp63 in mice leads to the formation of aggressive metastatic mammary adenocarcinoma at 9–16 months of age. Here we show that TAp63 is crucial for the transition of mammary cancer cells to TICs. When TAp63 is lost, MECs express embryonic and MaSC signatures and activate the Hippo pathway. These data indicate a crucial role for TAp63 in mammary TICs and provide a mechanism for its role as a tumor- and metastasis-suppressor in breast cancer.