A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

Kadye, Rose; Stoffels, Mihlali; Fanucci, Sidne; Mbanxa, Siso; Prinsloo, Earl

doi:10.3390/cells9041043

Cited by 12 publications

(12 citation statements)

References 224 publications

(304 reference statements)

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“…2D). Furthermore, DEGs associated with the adipocytokine signaling pathway, which regulates STAT3-mediated signals (Kadye et al, 2020), were also enriched in RGCs after ONT (Fig. 2D).…”

Section: Resultsmentioning

confidence: 99%

Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina

Chen

Lathrop

Kuwajima

et al. 2021

Preprint

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Visual information is transmitted from the eye to the brain along the optic nerve, a structure composed of retinal ganglion cell (RGC) axons. The optic nerve is highly vulnerable to damage in neurodegenerative diseases like glaucoma and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities and here, utilizing an optic nerve transection (ONT) injury and an RNA-seq-based approach, we identify genes and pathways active in RGCs that may modulate their survival. Through pharmacological perturbation, we demonstrate that JAK/STAT pathway activity is required for RGC survival after ONT. Furthermore, we show that immune responses directly contribute to RGC death after ONT; macrophages/microglia are recruited to the retina and blocking neuroinflammation or depleting these cells after ONT rescues survival of RGCs. Taken together, our results support a model in which pro-survival signals in RGCs, mediated by JAK/STAT signaling, counteract the activity of innate immune responses to modulate RGC vulnerability and resilience in the zebrafish retina after severe optic nerve damage.

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“…2D). Furthermore, DEGs associated with the adipocytokine signaling pathway, which regulates STAT3-mediated signals (Kadye et al, 2020), were also enriched in RGCs after ONT (Fig. 2D).…”

Section: Resultsmentioning

confidence: 99%

Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina

Chen

Lathrop

Kuwajima

et al. 2021

Preprint

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“…Beyond their important regulatory functions in immune response, STAT3 and NFκB family members are ubiquitously expressed in most types of cancer and involved in tumorigenesis, progressions and metastasis 47,48 . Moreover, sepsis is significantly associated with increased risk for many cancers including chronic myeloid leukaemia, myelodysplastic syndrome, acute myeloid leukaemia, cancers of the cervix, liver, lung, rectum and colon 49 .…”

Section: Discussionmentioning

confidence: 99%

Scaffold compound L971 exhibits anti‐inflammatory activities through inhibition of JAK/STAT and NFκB signalling pathways

Yan

Zhang

et al. 2021

J Cellular Molecular Medi

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JAK/STAT and NFκB signalling pathways play essential roles in regulating inflammatory responses, which are important pathogenic factors of various serious immune‐related diseases, and function individually or synergistically. To find prodrugs that can treat inflammation, we performed a preliminary high‐throughput screening of 18 840 small molecular compounds and identified scaffold compound L971 which significantly inhibited JAK/STAT and NFκB driven luciferase activities. L971 could inhibit the constitutive and stimuli‐dependent activation of STAT1, STAT3 and IκBα and could significantly down‐regulate the proinflammatory gene expression in mouse peritoneal macrophages stimulated by LPS. Gene expression profiles upon L971 treatment were determined using high‐throughput RNA sequencing, and significant differentially up‐regulated and down‐regulated genes were identified by DESeq analysis. The bioinformatic studies confirmed the anti‐inflammatory effects of L971. Finally, L971 anti‐inflammatory character was further verified in LPS‐induced sepsis shock mouse model in vivo. Taken together, these data indicated that L971 could down‐regulate both JAK/STAT and NFκB signalling activities and has the potential to treat inflammatory diseases such as sepsis shock.

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“…STAT3 is an important member of the signal transduction and activation protein (STAT) family ( Kadye et al, 2020 ). It is known to participate in the regulation of the transcription of multiple target genes related to the tumour occurrence and development, and cause abnormal expression of proteins related to proliferation, differentiation, cycle and apoptosis, thereby causing tumour cell anti-apoptosis, promoting cell proliferation and migration ( Sen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…We hope to screen out a bioactive components-enriched fraction from the studied stems and leaves of Dioscorea oppositifolia L. for developing an anti-NSCLC agent, because it has been well accepted that natural products with multi-components and multi-targets natures have advantages in managing the complex disease such as cancer (Su et al, 2017). STAT3 is an important member of the signal transduction and activation protein (STAT) family (Kadye et al, 2020). It is known to participate in the regulation of the transcription of multiple target genes related to the tumour occurrence and development, and cause abnormal expression of proteins related to proliferation, differentiation, cycle and apoptosis, thereby causing tumour cell anti-apoptosis, promoting cell proliferation and migration (Sen et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway

et al. 2021

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Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ERβ, and antagonising ERβ decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ERβ. However, after antagonizing ERβ, the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ERβ. In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ERβ-STAT3 signaling. Our ﬁndings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L.

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A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

Cited by 12 publications

References 224 publications

Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina

Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina

Scaffold compound L971 exhibits anti‐inflammatory activities through inhibition of JAK/STAT and NFκB signalling pathways

In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway

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