Int J Biol Sci 2023; 19(7):2006-2019. doi:10.7150/ijbs.79583 This issue Cite

Research Paper

Chronic stress promotes colorectal cancer progression by enhancing glycolysis through β2-AR/CREB1 signal pathway

Yunfeng Guan1#, Wang Yao2#, Hao Yu1, Ying Feng2, Yiyang Zhao1, Xiangyang Zhan3, Yan Wang1✉

1. Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
2. Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
3. Center of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
#These authors contributed equally to this work: Yunfeng Guan, Wang Yao

Citation:
Guan Y, Yao W, Yu H, Feng Y, Zhao Y, Zhan X, Wang Y. Chronic stress promotes colorectal cancer progression by enhancing glycolysis through β2-AR/CREB1 signal pathway. Int J Biol Sci 2023; 19(7):2006-2019. doi:10.7150/ijbs.79583. https://www.ijbs.com/v19p2006.htm
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Abstract

Graphic abstract

Colorectal cancer (CRC) is a common malignancy worldwide, and chronic stress has been considered as a significant risk factor for CRC. However, the role of chronic stress in CRC progression is unclear. The present study showed that pre-exposure to chronic stress facilitated CRC tumor growth in mice, and epinephrine promoted CRC cell proliferation in vitro. Metabolomics analysis revealed that chronic stress reshaped metabolic pathways to enhance glycolysis. Additional studies have shown that stress enhanced the expression levels of glycolytic-associated enzymes, including GLUT1, HK2 and PFKP. Mechanistically, chronic stress activated the β2-AR/PKA/CREB1 pathway, as a result, phosphorylated CREB1 transcriptional induced glycolytic enzymes expression. Furthermore, stress-induced cell proliferation and tumor growth could be reversed by administration of glycolysis inhibitor 2-deoxyglucose (2-DG) and β2-AR antagonist ICI118,551, respectively. Altogether, these findings define novel insights into the stress-induced epinephrine-mediated CRC progression from the point of view of tumor energy metabolism reprogramming and provide a perspective on targeting glycolysis as a potential approach in stress-associated CRC treatment.

Keywords: chronic stress, colorectal cancer, glycolysis, β2-AR, CREB1


Citation styles

APA
Guan, Y., Yao, W., Yu, H., Feng, Y., Zhao, Y., Zhan, X., Wang, Y. (2023). Chronic stress promotes colorectal cancer progression by enhancing glycolysis through β2-AR/CREB1 signal pathway. International Journal of Biological Sciences, 19(7), 2006-2019. https://doi.org/10.7150/ijbs.79583.

ACS
Guan, Y.; Yao, W.; Yu, H.; Feng, Y.; Zhao, Y.; Zhan, X.; Wang, Y. Chronic stress promotes colorectal cancer progression by enhancing glycolysis through β2-AR/CREB1 signal pathway. Int. J. Biol. Sci. 2023, 19 (7), 2006-2019. DOI: 10.7150/ijbs.79583.

NLM
Guan Y, Yao W, Yu H, Feng Y, Zhao Y, Zhan X, Wang Y. Chronic stress promotes colorectal cancer progression by enhancing glycolysis through β2-AR/CREB1 signal pathway. Int J Biol Sci 2023; 19(7):2006-2019. doi:10.7150/ijbs.79583. https://www.ijbs.com/v19p2006.htm

CSE
Guan Y, Yao W, Yu H, Feng Y, Zhao Y, Zhan X, Wang Y. 2023. Chronic stress promotes colorectal cancer progression by enhancing glycolysis through β2-AR/CREB1 signal pathway. Int J Biol Sci. 19(7):2006-2019.

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