CLOCK and BMAL1 stabilize and activate RHOA to promote F-actin formation in cancer cells.,Experimental & Molecular Medicine

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CLOCK and BMAL1 stabilize and activate RHOA to promote F-actin formation in cancer cells.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2018-Oct-04 , DOI: 10.1038/s12276-018-0156-4
Teng-Jiao Ma ₁ , Zhi-Wei Zhang ₁ , Yi-Lu Lu ₁ , Ying-Ying Zhang ₁ , Da-Chang Tao ₁ , Yun-Qiang Liu ₁ , Yong-Xin Ma ₁

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Circadian genes control most of the physiological functions in cancer cells, including cell proliferation, migration, and invasion. The CLOCK and BMAL1 complex plays a central role in circadian rhythms. Previous studies have shown that circadian genes may act as oncogenes or tumor-suppressor genes. In addition, F-actin, regulated by RHOA, has been shown to participate in tumor progression. However, the roles of the CLOCK and BMAL1 genes in the regulation of tumor progression via the RHOA-ROCK-CFL pathway remain largely unclear. Here we first indicate that the rearrangement of F-actin is regulated by CLOCK and BMAL1. We found that CLOCK and BMAL1 can upregulate RHOA expression by inhibiting CUL3-mediated ubiquitination and activate RHOA by reducing the interaction between RHOA and RhoGDI. Consequently, CLOCK and BMAL1 control the expression of the components of the RHOA-ROCK-CFL pathway, which alters the dynamics of F-actin/G-actin turnover and promotes cancer cell proliferation, migration, and invasion. In conclusion, our research proposes a novel insight into the role of CLOCK and BMAL1 in tumor cells.

中文翻译：

CLOCK 和 BMAL1 稳定并激活 RHOA，以促进癌细胞中 F-肌动蛋白的形成。

昼夜节律基因控制癌细胞的大部分生理功能，包括细胞增殖、迁移和侵袭。 CLOCK 和 BMAL1 复合体在昼夜节律中发挥着核心作用。先前的研究表明，昼夜节律基因可能充当癌基因或抑癌基因。此外，受 RHOA 调节的 F-肌动蛋白已被证明参与肿瘤进展。然而，CLOCK 和 BMAL1 基因在通过 RHOA-ROCK-CFL 途径调节肿瘤进展中的作用仍不清楚。在这里，我们首先指出F-肌动蛋白的重排是由CLOCK和BMAL1调节的。我们发现CLOCK和BMAL1可以通过抑制CUL3介导的泛素化来上调RHOA表达，并通过减少RHOA和RhoGDI之间的相互作用来激活RHOA。因此，CLOCK 和 BMAL1 控制 RHOA-ROCK-CFL 通路成分的表达，从而改变 F-肌动蛋白/G-肌动蛋白周转的动态并促进癌细胞增殖、迁移和侵袭。总之，我们的研究对 CLOCK 和 BMAL1 在肿瘤细胞中的作用提出了新的见解。

更新日期：2019-01-26

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