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p190A 失活突变导致异常的 RhoA 激活，并通过 Hippo-YAP 通路促进子宫内膜癌的恶性转化。

p190A inactivating mutations cause aberrant RhoA activation and promote malignant transformation via the Hippo-YAP pathway in endometrial cancer.

机构信息

Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China.

Department of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.

出版信息

Signal Transduct Target Ther. 2020 May 27;5(1):81. doi: 10.1038/s41392-020-0170-6.

DOI:10.1038/s41392-020-0170-6
PMID:32457342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7250911/
Abstract

The Rho family of GTPases is strictly regulated by a large family of GTPase-activating proteins (GAPs) that stimulate the relatively weak intrinsic GTP-hydrolyzing activity of Rho GTPases. p190A is a potent and widely expressed GAP that acts on RhoA GTPases. p190A is frequently mutated in endometrial cancer, but the contribution of p190A mutations to endometrial tumorigenesis remains unclear. Here we identified that p190A is an upstream regulator of the Hippo-YAP signaling pathway, which is a critical regulator of cell proliferation, apoptosis, and cell fate. p190A knockout in endometrial cancer cells promoted cell proliferation, migration, and epithelial-mesenchymal transition (EMT), which were partially dependent on YAP activation. Wild-type p190A, but not endometrial cancer-associated mutants, suppressed the nuclear localization, transcriptional activity, and malignant transformation function of YAP. Moreover, the nuclear localization of YAP was enhanced in p190A-mutated endometrial cancer. These findings reveal novel molecular mechanisms underlying Hippo-YAP pathway-driven endometrial tumorigenesis and elucidate the potential for therapy targeting the Hippo-YAP pathway in p190A-mutated endometrial cancer.

摘要

Rho 家族的 GTPases 受到一大类 GTPase 激活蛋白 (GAPs) 的严格调控，这些 GAPs 可刺激 Rho GTPases 相对较弱的内在 GTP 水解活性。p190A 是一种有效的、广泛表达的 GAP，可作用于 RhoA GTPases。p190A 在子宫内膜癌中经常发生突变，但 p190A 突变对子宫内膜肿瘤发生的贡献尚不清楚。在这里，我们确定 p190A 是 Hippo-YAP 信号通路的上游调节剂，该通路是细胞增殖、凋亡和细胞命运的关键调节剂。子宫内膜癌细胞中 p190A 的敲除促进了细胞增殖、迁移和上皮-间充质转化 (EMT)，部分依赖于 YAP 的激活。野生型 p190A，但不是与子宫内膜癌相关的突变体，抑制了 YAP 的核定位、转录活性和恶性转化功能。此外，p190A 突变的子宫内膜癌中 YAP 的核定位增强。这些发现揭示了 Hippo-YAP 通路驱动子宫内膜肿瘤发生的新分子机制，并阐明了针对 Hippo-YAP 通路在 p190A 突变的子宫内膜癌中治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/5e1937b6f4a6/41392_2020_170_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/1578bd3753cb/41392_2020_170_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/545c8b211912/41392_2020_170_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/0e53f744d18e/41392_2020_170_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/6eb101a6ddc1/41392_2020_170_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/6980d6d25f05/41392_2020_170_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/5e1937b6f4a6/41392_2020_170_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/1578bd3753cb/41392_2020_170_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/545c8b211912/41392_2020_170_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/0e53f744d18e/41392_2020_170_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/6eb101a6ddc1/41392_2020_170_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/6980d6d25f05/41392_2020_170_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d778/7250911/5e1937b6f4a6/41392_2020_170_Fig6_HTML.jpg

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本文引用的文献

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mA 去甲基化酶 FTO 和 ALKBH5 通过共同调节 ARHGAP35 加重鼻咽癌的恶性进展。
Cell Death Discov. 2024 Jan 23;10(1):43. doi: 10.1038/s41420-024-01810-0.
4
The Hippo pathway in endometrial cancer: a potential therapeutic target?子宫内膜癌中的河马通路：一个潜在的治疗靶点？
Front Oncol. 2023 Oct 20;13:1273345. doi: 10.3389/fonc.2023.1273345. eCollection 2023.
5
Extracellular matrix stiffness mediates uterine repair via the Rap1a/ARHGAP35/RhoA/F-actin/YAP axis.细胞外基质硬度通过 Rap1a/ARHGAP35/RhoA/F-actin/YAP 轴介导子宫修复。
Cell Commun Signal. 2023 Jan 23;21(1):22. doi: 10.1186/s12964-022-01018-8.
6
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7
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Cell Death Dis. 2022 Sep 10;13(9):783. doi: 10.1038/s41419-022-05224-7.
8
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Front Mol Biosci. 2022 Jul 1;9:929832. doi: 10.3389/fmolb.2022.929832. eCollection 2022.
9
The deadly cross-talk between Hippo pathway and epithelial-mesenchymal transition (EMT) in cancer.肿瘤中 Hippo 通路与上皮-间充质转化（EMT）的致命串扰。
Mol Biol Rep. 2022 Oct;49(10):10065-10076. doi: 10.1007/s11033-022-07590-z. Epub 2022 May 23.
10
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Front Cell Dev Biol. 2022 May 5;10:890419. doi: 10.3389/fcell.2022.890419. eCollection 2022.