ArticleCell death & disease2021
Immune and nonimmune mechanisms mediate the mental stress-induced tumor growth in a xenograft model of breast cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- A systematic review and exploration of clinical application of liver depression syndrome in breast cancer.Frontiers in oncology · 2025Pooled it
- Long-term impact of stressful life events on breast cancer risk: A 36-year genetically informed prospective study in the Finnish Twin Cohort.International journal of cancer · 2026Article
- Chronic stress: a fourth etiology in tumorigenesis?Molecular cancer · 2025Review
- Single-cell RNA sequencing reveals the effects of mental stress on mouse mammary tumors and the tumor microenvironment.Cell death discovery · 2025Article
- Association between olanzapine and immune function in lung cancer patients with anxiety and depression: a retrospective cohort study of medical records.Frontiers in psychiatry · 2025Article
- Development and Validation of a Comprehensive Prognostic and Depression Risk Index for Gastric Adenocarcinoma.International journal of molecular sciences · 2024Article
- Chronic stress in solid tumor development: from mechanisms to interventions.Journal of biomedical science · 2023Review
- IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer.Theranostics · 2023Article
- Stress, psychiatric disease, and obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.Obesity pillars · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excess mental stress may harm health, and even accelerate cancer initiation and progression. One fourth of breast cancer patients suffer mental stress including anxiety, sadness, or depression, which negatively affect prognosis and survival. However, the regulatory mechanism is yet to be determined. Herein, we applied unpredictable stress stimuli to the breast tumor-bearing mice to establish a xenograft model of breast cancer suffering mental stress, followed by behavioral tests, tumor growth tracking, immune analysis, miRNA screening, and tumor cell proliferation analysis as well. As a result, increased stress hormone levels in serum, decreased percentage of T and NK cells in both blood and tumor samples and accelerated tumor growth in vivo were observed in the mice exposed to mental stress. Promoted cell proliferation was observed in both primary tumor cells derived from the stressed mice and 4T1 breast cancer cells treated with stress hormone corticosterone. In addition, a subset of miRNAs including miR-326, 346, 493, 595, 615, and 665 were identified through a miRNA screening with downregulation in tumors of the stressed mice. CCND1 was identified as a common target gene of miR-346 and miR-493, the top two most significantly downregulated miRNAs by stress exposure. The stress-miRNA-CCND1 signaling regulation of the tumor cell proliferation was further validated in 4T1 cells treated with corticosterone in vitro. GO terms and KEGG pathways analyses on the target genes of miR-346 and miR-493 revealed their involvement in the regulation of human cancer and neuron system, indicating the importance of non-coding genome in mediating the mental stress-induced cancer regulation. In conclusion, this study not only explored immune and nonimmune mechanisms through which mental stress exposure contributes to tumor growth in breast cancer, but also suggested a new therapeutic strategy for cancer patients suffering mental stress.
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