Li Xiaoxue, Wang Siyang, Yang Shuhong, Ying Junjie, Yu Hang, Yang Chunlei, Liu Yanyou, Wang Yuhui, Cheng Shuting, Xiao Jing, Guo Huiling, Jiang Zhou, Wang Zhengrong
Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Department of Life Sciences, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Oncol Lett. 2018 May;15(5):7097-7103. doi: 10.3892/ol.2018.8226. Epub 2018 Mar 9.
The circadian rhythm regulates numerous physiological activities, including sleep and wakefulness, behavior, immunity and metabolism. Previous studies have demonstrated that circadian rhythm disorder is associated with the occurrence of tumors. Responsible for regulating a number of functions, the Circadian locomotor output cycles kaput () gene is one of the core regulatory genes of circadian rhythm. The gene has also been implicated in the occurrence and development of tumors in previously studies. The present study evaluated the role of the gene in the proliferation and migration of mouse breast cancer 4T1 cells, and investigated its possible regulatory pathways and mechanisms. It was reported that downregulation of facilitated the proliferation and migration of breast cancer cells. Further investigation revealed the involvement of IQ motif containing GTPase activating protein 1 (IQGAP1) protein expression in the regulatory pathway, further influencing the expression of E-cadherin, a known proprietor of tumor cell migration and invasion. To the best of our knowledge, the present study is the first to report that , acting through the regulation of the scaffolding protein IQGAP1, regulates the downstream expression of E-cadherin, thereby affecting tumor cell structure and motility. These results confirmed the role of in breast cancer tumor etiology and provide insight regarding the molecular avenues of its regulatory nature, which may translate beyond breast cancer into other known functions of the gene.
昼夜节律调节众多生理活动,包括睡眠和觉醒、行为、免疫和代谢。先前的研究表明,昼夜节律紊乱与肿瘤的发生有关。昼夜运动输出周期失效(CLOCK)基因负责调节多种功能,是昼夜节律的核心调节基因之一。先前的研究也表明该基因与肿瘤的发生和发展有关。本研究评估了CLOCK基因在小鼠乳腺癌4T1细胞增殖和迁移中的作用,并研究了其可能的调控途径和机制。据报道,CLOCK基因的下调促进了乳腺癌细胞的增殖和迁移。进一步的研究揭示了含IQ模体的GTP酶激活蛋白1(IQGAP1)蛋白表达参与了CLOCK调控途径,进而影响E-钙黏蛋白的表达,E-钙黏蛋白是已知的肿瘤细胞迁移和侵袭的调控因子。据我们所知,本研究首次报道CLOCK基因通过调节支架蛋白IQGAP1,调控E-钙黏蛋白的下游表达,从而影响肿瘤细胞的结构和运动性。这些结果证实了CLOCK基因在乳腺癌肿瘤病因学中的作用,并为其调控性质的分子途径提供了见解,这可能不仅适用于乳腺癌,还适用于该基因的其他已知功能。