Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion.
Epigenetic activation of the small GTPase TCL contributes to colorectal cancer cell migration and invasion.
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小GTP酶TCL的表观遗传激活有助于结直肠癌细胞迁移和侵袭
DOI：
10.1038/s41389-020-00269-9
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发表时间：
2020-09-30
期刊：
影响因子：
6.2
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Chen B;Fan Z;Sun L;Chen J;Feng Y;Fan X;Xu Y
TC 10样（TCL）是一种小的GT酶，与致癌作用有关。在许多不同类型的癌症中观察到TCL表达升高，尽管对潜在的表观遗传机制知之甚少。在这里，我们报告TCL上调与人类结直肠癌活检标本和培养的结直肠癌细胞的高度恶性相关。缺氧，一个促转移刺激，上调TCL在HT-29细胞中的表达。进一步的研究发现肌心蛋白相关转录因子A（MRTF-A）以TCL依赖的方式促进HT-29细胞的迁移和侵袭。MRTF-A在缺氧时直接结合近端TCL启动子以激活TCL转录。染色质免疫沉淀（ChIP）分析表明，低氧刺激特异性地增强TCL启动子周围组蛋白H4 K16的乙酰化，而MRTF-A的缺失或抑制则可消除这种乙酰化。在机制上，MRTF-A与H4 K16乙酰转移酶hMOF相互作用并将其募集至TCL启动子以协同调节TCL转录。hMOF去除或抑制减弱缺氧诱导的HT-29细胞TCL表达和迁移/侵袭。总之，我们的数据确定了一个新的MRTF-A-hMOF-TCL轴，有助于结直肠癌转移。
TC10-like (TCL) is a small GTPase that has been implicated in carcinogenesis. Elevated TCL expression has been observed in many different types of cancers although the underlying epigenetic mechanism is poorly understood. Here we report that TCL up-regulation was associated with high malignancy in both human colorectal cancer biopsy specimens and in cultured colorectal cancer cells. Hypoxia, a pro-metastatic stimulus, up-regulated TCL expression in HT-29 cells. Further studies revealed that myocardin-related transcription factor A (MRTF-A) promoted migration and invasion of HT-29 cells in a TCL-dependent manner. MRTF-A directly bound to the proximal TCL promoter in response to hypoxia to activate TCL transcription. Chromatin immunoprecipitation (ChIP) assay showed that hypoxia stimulation specifically enhanced acetylation of histone H4K16 surrounding the TCL promoter, which was abolished by MRTF-A depletion or inhibition. Mechanistically, MRTF-A interacted with and recruited the H4K16 acetyltransferase hMOF to the TCL promoter to cooperatively regulate TCL transcription. hMOF depletion or inhibition attenuated hypoxia-induced TCL expression and migration/invasion of HT-29 cells. In conclusion, our data identify a novel MRTF-A-hMOF-TCL axis that contributes to colorectal cancer metastasis.
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影响因子：
8
作者：
Hermanns, C.;Hampl, V.;Muehlich, S.
通讯作者：
Muehlich, S.
转录因子p300和MRTF-A协同增强MCF-7乳腺癌细胞迁移相关基因的表达
DOI：
10.1016/j.bbrc.2015.10.060
发表时间：
2015-11-27
影响因子：
3.1
作者：
He, Hongpeng;Wang, Dandan;Zhang, Tong-Cun
通讯作者：
Zhang, Tong-Cun
影响因子：
3.9
作者：
Kim C;Yang H;Park I;Chon HJ;Kim JH;Kwon WS;Lee WS;Kim TS;Rha SY
通讯作者：
Rha SY
影响因子：
--
作者：
Jaganathan, Anbalagan;Chaurasia, Pratima;Mujtaba, Shiraz
通讯作者：
Mujtaba, Shiraz
影响因子：
5.2
作者：
Kim, Jeffrey J.;Khalid, Omar;Namazi, AmirHosien;Tu, Thanh G.;Elie, Omid;Lee, Connie;Kim, Yong
通讯作者：
Kim, Yong