Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions

El‐Tanani, Mohamed; Khatib, Arwa Omar Al; Aladwan, Safwan M.; Abuelhana, Ahmed; McCarron, Paul A.; Tambuwala, Murtaza M.

doi:10.1016/j.cellsig.2022.110275

Cited by 54 publications

(29 citation statements)

References 98 publications

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“…STAT3 is a polymorphic transcription factor involved in a range of physiological and pathophysiological processes, including inflammation, cell growth, proliferation, and differentiation [ 20 , 21 , 22 , 23 ]. STAT3 has been shown to induce the expression of multiple fibrotic genes and can transduce the pro-fibrotic effects of TGF-β from the cell surface to the nucleus.…”

Section: Introductionmentioning

confidence: 99%

β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression

Sun

Kim

Byon

et al. 2022

IJMS

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Renal fibrosis is a chronic pathological process that seriously endangers human health. However, the current therapeutic options for this disease are extremely limited. Previous studies have shown that signaling factors such as JAK2/STAT3, Smad3, and Myd88 play a regulatory role in renal fibrosis, and β-elemene is a plant-derived sesquiterpenoid organic compound that has been shown to have anti-inflammatory, anti-cancer, and immunomodulatory effects. In the present study, the anti-fibrotic effect of β-elemene was demonstrated by in vivo and in vitro experiments. It was shown that β-elemene inhibited the synthesis of extracellular matrix-related proteins in unilateral ureteral obstruction mice, and TGF-β stimulated rat interstitial fibroblast cells, including α-smooth muscle actin, vimentin, and connective tissue growth factor, etc. Further experiments showed that β-elemene reduced the expression levels of the above-mentioned fibrosis-related proteins by blocking the phosphorylation of JAK2/STAT3, Smad3, and the expression or up-regulation of MyD88. Notably, knockdown of MyD88 attenuated the phosphorylation levels of STAT3 and Smad3 in TGF-β stimulated NRK49F cell, which may be a novel molecular mechanism by which β-elemene affects renal interstitial fibrosis. In conclusion, this study elucidated the anti-interstitial fibrosis effect of β-elemene, which provides a new direction for future research and development of drugs related to chronic kidney disease.

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Section: Introductionmentioning

confidence: 99%

β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression

Sun

Kim

Byon

et al. 2022

IJMS

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“…The NF-κB signaling pathway promotes invasion and metastasis of NSCLC by enhancing the activation of FAK, a key kinase of focal adhesion [20]. And constitutionally activated STAT3 signaling pathways in many cancers contribute to many markers of carcinogenesis and metastasis, including promoting tumor cell proliferation and enhancing the ability of cells to migrate and invade into extracellular matrix [21]. Invasion into the extracellular matrix is one of the key steps in tumor metastasis.…”

Section: Discussionmentioning

confidence: 99%

Establishment of metastasis-related prognostic models for colon cancer and bioinformatics analysis of the benefits of aspirin chemoprophylaxis

Shen

Jiang

et al. 2022

Preprint

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Background: Invasion and metastasis are the main factors affecting the prognosis of patients with colorectal cancer. Therefore, it is urgent to explore the key metastasis genes and potential regulatory mechanisms that affect the prognosis of colorectal cancer, and provide new prognostic markers or therapeutic targets for colorectal cancer.Methods: Firstly, we obtained differentially expressed metastasis-related genes in cancer and normal tissues. By constructing WGCNA from differentially expressed genes, the modules most associated with colon cancer were identified. Univariate and lasso-cox regression analyses were used to identify key prognostic genes for the most relevant modules and to establish a risk score model. Nomogram model was constructed to predict OS of colon cancer patients by risk score. GO and KEGG enrichment analysis were performed to study the pathways and functions of these module genes. Iregulon plugin in cytoscape was used to explore the transcription factors of module genes. Finally, aspirin interacting genes were obtained through the Comparative Toxicology Genomics Database, and the clinical significance of aspirin regulation on these genes was clarified.Results: 2062 metastasis-related genes were involved in the construction of WGCNA, blue and yellow modules were significantly correlated with colon cancer. Analysis of GO and KEGG pathways of these two modules showed that the function of differential genes is closely related to many important processes in tumor genesis and metastasis. We used the blue module gene to build a risk score model that predicted overall survival (OS). In addition, nomogram combining risk score with age, stage, and M-stage were developed to better predict 1-, 3-, and 5-year survival. Transcription factor analysis showed that E2F family were the key regulator of blue module, while NFκB1 and STAT3 were the key transcription factors of yellow module. Finally, we identified that patients of colon cancer whose NOX4, CXCL8, CXCL5, GDF15, and MMP13 genes were continuously upregulated may not be suitable for aspirin chemoprophylaxis.Conclusions: We developed and validated a predictive model of metastasis genes. Patients with colon cancer whose NOX4, CXCL8, CXCL5, GDF15, and MMP13 genes are upregulated may not be ideal candidates for aspirin chemoprophylaxis.

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“…Esophageal cancer was an inflammatory tumor ( 99 ). The Stat3 gene product is at the intersection of many cancer and inflammatory signaling pathways ( 100 ). Therefore, it was possible that the mechanism of action of metformin in esophageal cancer was related to Stat3 .…”

Section: Metformin As An Antitumor Candidate Drugmentioning

confidence: 99%

Metformin: A promising drug for human cancers (Review)

Huang

Zhao

et al. 2022

Oncol Lett

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Small-molecule chemical drugs are of great significance for tumor-targeted and individualized therapies. However, the development of new small-molecule drugs, from basic experimental research and clinical trials to final application in clinical practice, is a long process that has a high cost. It takes at least 5 years for most drugs to be developed in the laboratory to prove their effectiveness and safety. Compared with the development of new drugs, repurposing traditional non-tumor drugs can be a shortcut. Metformin is a good model for a new use of an old drug. In recent years, the antitumor efficacy of metformin has attracted much attention. Epidemiological data and in vivo , and in vitro experiments have shown that metformin can reduce the incidence of cancer in patients with diabetes and has a strong antagonistic effect on metabolism-related tumors. Recent studies have shown that metformin can induce autophagy in esophageal cancer cells, mainly by inhibiting inflammatory signaling pathways. In recent years, studies have shown that the antitumor functions and mechanisms of metformin are multifaceted. The present study aims to review the application of metformin in tumor prevention and treatment.

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Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions

Cited by 54 publications

References 98 publications

β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression

β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression

Establishment of metastasis-related prognostic models for colon cancer and bioinformatics analysis of the benefits of aspirin chemoprophylaxis

Metformin: A promising drug for human cancers (Review)

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