Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer

Du, Peixin; Zeng, Hao; Xiao, Yu; Zhao, Ying; Zheng, Bo; Deng, Yao; Liu, Jie; Huang, Boyen; Zhang, Xinyao; Yang, Kuo-Hsin; Jiang, Yu; Ma, Xuelei

doi:10.1038/s41419-020-02981-1

Cited by 53 publications

(50 citation statements)

References 59 publications

(68 reference statements)

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“…It is reported that diphenyl urea derivative could serve as an inhibitor on human lung cancer cell migration by disrupting EMT via Wnt/β-catenin and PI3K/Akt signaling ( 44 ). Research from Du et al demonstrated that chronic stress promotes EMT-mediated metastasis through activation of the STAT3 signaling pathway by miR-337-3p in breast cancer ( 45 ). The EMT signaling pathway, as an axis center, has been revealed to largely participate in the regulation of cancer metastasis ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway

et al. 2020

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Breast cancer which is the most common type of diagnosed cancer among women worldwide possesses metastatic potential, multi-drug resistance, and high mortality. The NF-κB signaling pathway has been revealed to be abnormally activated in breast cancer cells and closely associated with high metastasis and poor prognosis. In the present study, it was reported that chlorogenic acid (CGA), a potent NF-κB inhibitor derived from coffee, exerted antitumor activity in breast cancer. MTT and colony formation assays were conducted and it was revealed that CGA inhibited viability and proliferation in breast cancer cells. Additionally, CGA significantly induced apoptosis and suppressed migration and invasion in breast cancer cells. Notably, immunofluorescence analysis confirmed that CGA could efficiently suppress nuclear transcription of NF-κB p65. In addition, results of western blotting demonstrated that CGA markedly impaired the NF-κB and EMT signaling pathways. The antitumor effect of CGA was evaluated in a subcutaneous tumor mouse model of 4T1 cells, and the results revealed that CGA markedly retarded tumor growth and prolonged the survival rate of tumor-bearing mice. Notably, CGA inhibited pulmonary metastasis of 4T1 cells by enhancing the proportion of CD4 + and CD8 + T cells in spleens of mice, which indicated an improvement of antitumor immunity. In conclusion, the present present study demonstrated that CGA improved antitumor immunity, exerting antitumor and anti-metastatic effects by impairing the NF-κB/EMT signaling pathway, suggesting that CGA may serve as a potential candidate for therapy of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway

et al. 2020

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“…When going for holistic cancer care [ 97 , 98 ], spiritual and emotional conditions are equally essential, alongside physical and social status ( Figure 7 ). Psychosocial stress is associated with cancer incidence [ 98 , 99 , 100 ], metastasis [ 99 , 101 , 102 , 103 ], and poor survival [ 104 ]. These impacts might be mediated through the hypothalamic–pituitary–adrenal (HPA) axis [ 105 ].…”

Section: Discussionmentioning

confidence: 99%

A Transcriptomic Analysis of Head and Neck Squamous Cell Carcinomas for Prognostic Indications

Chi

Hsiao

et al. 2021

JPM

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Survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method for discovering gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). A cutoff point is usually used in survival analysis for patient dichotomization when using continuous gene expression values. There is some optimization software for cutoff determination. However, the software’s predetermined cutoffs are usually set at the medians or quantiles of gene expression values. There are also few clinicopathological features available in pre-processed datasets. We applied an in-house workflow, including data retrieving and pre-processing, feature selection, sliding-window cutoff selection, Kaplan–Meier survival analysis, and Cox proportional hazard modeling for biomarker discovery. In our approach for the TCGA HNSCC cohort, we scanned human protein-coding genes to find optimal cutoff values. After adjustments with confounders, clinical tumor stage and surgical margin involvement were found to be independent risk factors for prognosis. According to the results tables that show hazard ratios with Bonferroni-adjusted p values under the optimal cutoff, three biomarker candidates, CAMK2N1, CALML5, and FCGBP, are significantly associated with overall survival. We validated this discovery by using the another independent HNSCC dataset (GSE65858). Thus, we suggest that transcriptomic analysis could help with biomarker discovery. Moreover, the robustness of the biomarkers we identified should be ensured through several additional tests with independent datasets.

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“…All the mice received three kinds of behavior tests within the two weeks after the last stress stimulation, including the open field test, the tail suspension test and the sucrose preference test, following the procedures described in the literature [ 32 , 33 ]. A video tracking system (SuperMaze V2.0, Shanghai, China) was used to record and analyze the activity of mice in the open field test and tail suspension test.…”

Section: Methodsmentioning

confidence: 99%

Immune and nonimmune mechanisms mediate the mental stress-induced tumor growth in a xenograft model of breast cancer

Liu

Zheng

et al. 2021

Cell Death Dis

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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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Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer

Cited by 53 publications

References 59 publications

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway

Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF‑κB signaling pathway

A Transcriptomic Analysis of Head and Neck Squamous Cell Carcinomas for Prognostic Indications

Immune and nonimmune mechanisms mediate the mental stress-induced tumor growth in a xenograft model of breast cancer

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