Role of STAT3 signaling pathway in breast cancer

Ma, Jiahui; Qin, Li; Li, Xia

doi:10.1186/s12964-020-0527-z

Cited by 267 publications

(194 citation statements)

References 116 publications

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“…10 STAT3 plays crucial roles in cell proliferation, survival and differentiation, and has been shown to be persistently activated in a high percentage of malignancies, including TNBC. 11,12 Therefore, the involvement of the Akt/mTOR and STAT3 signaling pathways in the molecular mechanisms underlying the effects of BA were investigated.…”

Section: Introductionmentioning

confidence: 99%

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

Zhao

Lin

Mok

et al. 2020

OTT

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Purpose: Triple-negative breast cancer (TNBC) is a a breast cancer subtype characterized by a lack of estrogen receptor, progesterone receptor and human epidermal growth receptor 2 and is associated with poorer prognoses when compared to other breast cancers. Thus, novel anti-cancer agents with high efficacy are urgently needed. Brevilin A (BA), a natural sesquiterpene lactone, has been reported to exhibit anti-cancer effects. However, the effects of BA on TNBC have not yet been demonstrated. In this study, we investigated the anti-TNBC effects and the underlying mechanism of BA, in vitro and in vivo. Methods: Two TNBC cell lines and a xenograft mouse model were employed to assess the effects of BA. Cell viability was detected by MTT assay. Cell cycle status and apoptosis were evaluated by flow cytometry. Cell migration was measured by wound-healing assay. Protein expression was measured by Western blotting analysis. The in vivo anti-cancer activity of BA was assessed in orthotopic tumor xenograft mice. Results: BA significantly inhibited the growth of TNBC cells in a dose-and time-dependent manner via induction of cell cycle arrest at G2/M phase arrest and apoptosis. BA also inhibited tumor cell migration. BA significantly downregulated the expression of Akt, mTOR, Stat3 and their phosphorylation, and thus inhibiting the activation of the Akt/mTOR and STAT3 signaling pathways. Furthermore, oral administration of BA at 25 or 50 mg/kg leads to significant inhibition of tumor growth and proliferation in tumor xenograft model mice. Conclusion: BA significantly inhibited the growth and migration of TNBC cells, and induced cell cycle arrest and apoptosis. These inhibitory effects were associated with the suppression of the Akt/mTOR and Stat3 signal pathways. Based on our findings, BA possesses a promising candidate for development as an anti-cancer therapeutic drug against TNBC.

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Section: Introductionmentioning

confidence: 99%

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

Zhao

Lin

Mok

et al. 2020

OTT

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“…STAT3 is an important transcription factor. Its overexpression and constitutive activation play a key role in the progression, proliferation and metastasis of breast cancer 14 . Therefore, expression levels of STAT3 and p-STAT3 were examined by Western-blotting after AD treatment.…”

Section: Resultsmentioning

confidence: 99%

Arnicolide D Inhibits Triple Negative Breast Cancer Cell Proliferation by Suppression of Akt/mTOR and STAT3 Signaling Pathways

Zhao¹,

Lin²,

Mok³

et al. 2020

Int. J. Med. Sci.

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Triple-Negative Breast Cancer (TNBC) is a most dangerous breast cancer subtype. The naturally occurring sesquiterpene lactone, arnicolide D (AD), has proven effective against a variety of tumors, however, the inhibitory effects of AD against TNBC and the underlying mechanisms remain unclear. In the present study, two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and an MDA-MB-231 xenograft mouse model were employed to investigate the anti-TNBC effects of AD in vitro and in vivo . Cell viability was assessed by MTT assay. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by immunoblotting. In vitro studies demonstrated that AD significantly decreased cell viability, and induced G2/M cell cycle arrest and apoptosis. In vivo assays showed that oral administration of 25 or 50 mg/kg AD for 22 days led to a reduction of tumor weights by 24.7% or 41.0%, without appreciable side effects. Mechanistically, AD inhibited the activation of Akt/mTOR and STAT3 signaling pathways. Based on our findings, AD is a promising candidate for development as an adjunctive therapeutic drug for TNBC.

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“…Additionally, STAT3 acts as an oncogene in numerous types of cancer, including breast (18), lung (19) and pancreatic cancer (20). Constitutive activation of STAT3 was first observed to be associated with oncogenic transformation by the viral Src oncoprotein (21).…”

Section: Stat3 Is a Key Molecule In The Oncogenic Behavior Of Diffusementioning

confidence: 99%

STAT3 is a key molecule in the oncogenic behavior of diffuse intrinsic pontine glioma

et al. 2020

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Diffuse intrinsic pontine glioma (DIPG) is one of the most lethal childhood brain tumors. This tumor is unique because it is detected exclusively in the ventral pons of patients aged between 6 and 7 years, which suggests a developmental nature of its formation. Signal transducer and activator of transcription 3 (STAT3) is a critical molecule for the differentiation of neural stem cells into astrocytes during neurodevelopment. Additionally, STAT3 is associated with oncogenesis and the epithelial-mesenchymal transition (EMT) in various types of tumor. In recent years, several studies have demonstrated the oncogenic role of STAT3 in high-grade gliomas. However, the role of STAT3 in DIPG at the cellular level remains unknown. To assess the possible association between gliogenesis and DIPG, the expression levels of various molecules participating in the differentiation of neural stem cells were compared between normal brain control tissues and DIPG tissues using open public data. All of the screened genes exhibited significantly increased expression in DIPG tissues compared with normal tissues. As STAT3 expression was the most increased, the effect of STAT3 inhibition in a DIPG cell line was assessed via STAT3 short hairpin (sh)RNA transfection and treatment with AG490, a STAT3 inhibitor. Changes in viability, apoptosis, EMT and radiation therapy efficiency were also evaluated. Downregulation of STAT3 resulted in decreased cyclin D1 expression and cell viability, migration and invasion. Additionally, treatment with STAT3 shRNA or AG490 suppressed the EMT phenotype. Finally, when radiation was administered in combination with STAT3 inhibition, the therapeutic efficiency, assessed by cell viability and DNA damage repair, was increased. The present results suggest that STAT3 is a potential therapeutic target in DIPG, especially when combined with radiation therapy.

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Role of STAT3 signaling pathway in breast cancer

Cited by 267 publications

References 116 publications

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

<p>Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways</p>

Arnicolide D Inhibits Triple Negative Breast Cancer Cell Proliferation by Suppression of Akt/mTOR and STAT3 Signaling Pathways

STAT3 is a key molecule in the oncogenic behavior of diffuse intrinsic pontine glioma

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