LEPR/FOS/JUNB signaling pathway contributes to chronic restraint stress-induced tumor proliferation

Jian Zhu; Qing Liu; Shuang Nie; Yanan Huang; Linjing Zhao; Fengfeng Mo

doi:10.1016/j.bbrc.2024.150042

LEPR/FOS/JUNB signaling pathway contributes to chronic restraint stress-induced tumor proliferation

Biochem Biophys Res Commun. 2024 May 6:719:150042. doi: 10.1016/j.bbrc.2024.150042. Online ahead of print.

Authors

Jian Zhu¹, Qing Liu², Shuang Nie², Yanan Huang², Linjing Zhao³, Fengfeng Mo⁴

Affiliations

¹ School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai, 201620, China; Department of Naval Nutrition and Food Hygiene, Naval Medical University, Shanghai, 200433, China.
² Department of Naval Nutrition and Food Hygiene, Naval Medical University, Shanghai, 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
³ School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai, 201620, China. Electronic address: ljzhao@sues.edu.cn.
⁴ Department of Naval Nutrition and Food Hygiene, Naval Medical University, Shanghai, 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China. Electronic address: mofengfeng@smmu.edu.cn.

PMID: 38761633
DOI: 10.1016/j.bbrc.2024.150042

Abstract

Background & aims: Psychosocial stress has become an unavoidable part of life, which was reported to promote tumor development. Chronic stress significantly promotes the norepinephrine (NE) secretion and the expression of leptin receptor (LEPR), leading to tumor invasion, metastasis, and proliferation. However, the mechanism of chronic stress-induced tumor proliferation remains unclear.

Methods: To reveal the effect of chronic stress on tumor proliferation, subcutaneous tumor models combined with chronic restraint stress (CRS) were established. Combined with the transcript omics database of liver cancer patients, the target pathways were screened and further verified by in vitro experiments.

Results: The results showed that the CRS with subcutaneous tumor transplantation (CRS + tumor) group exhibited significantly larger tumor sizes than the subcutaneous tumor transplantation (tumor) group. Compared with the tumor group, CRS obviously increased the mRNA levels of LEPR, FOS, and JUNB of tumor tissues in the CRS + tumor group. Furthermore, the treatment with norepinephrine (NE) significantly elevated the survival rate of H22 cells and enhanced the expression of LEPR, FOS, and JUNB in vitro. Silencing LEPR significantly reduced the expression of FOS and JUNB, accompanied by a decrease in H22 cell viability.

Conclusions: Our study demonstrated that CRS activates the LEPR-FOS-JUNB signaling pathway by NE, aggravating tumor development. These findings might provide a scientific foundation for investigating the underlying pathological mechanisms of tumors in response to chronic stress.

Keywords: Chronic restraint stress; Leptin receptor; Liver cancer; Norepinephrine.