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. 2024 Jul 30:719:150042.
doi: 10.1016/j.bbrc.2024.150042. Epub 2024 May 6.

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

Jian Zhu  1 , Qing Liu  2 , Shuang Nie  2 , Yanan Huang  2 , Linjing Zhao  3 , Fengfeng Mo  4
Affiliations

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

Jian Zhu et al. Biochem Biophys Res Commun. .

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.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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