Circadian locomotor output cycles kaput affects the proliferation and migration of breast cancer cells by regulating the expression of E-cadherin via IQ motif containing GTPase activating protein 1

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

doi:10.3892/ol.2018.8226

Circadian locomotor output cycles kaput affects the proliferation and migration of breast cancer cells by regulating the expression of E-cadherin via IQ motif containing GTPase activating protein 1

Authors:
- Xiaoxue Li
- Siyang Wang
- Shuhong Yang
- Junjie Ying
- Hang Yu
- Chunlei Yang
- Yanyou Liu
- Yuhui Wang
- Shuting Cheng
- Jing Xiao
- Huiling Guo
- Zhou Jiang
- Zhengrong Wang
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Affiliations: 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
Published online on: March 9, 2018 https://doi.org/10.3892/ol.2018.8226
Pages: 7097-7103
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 (Clock) gene is one of the core regulatory genes of circadian rhythm. The Clock gene has also been implicated in the occurrence and development of tumors in previously studies. The present study evaluated the role of the Clock 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 Clock 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 Clock 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 Clock, 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 Clock 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.

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