Differentiated glioma cell-derived fibromodulin activates integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth

Sengupta, Shreoshi; Mondal, Mainak; Prasasvi, Kaval Reddy; Mukherjee, Arani; Magod, Prerna; Urbach, Serge; Friedmann‐Morvinski, Dinorah; Marin, Philippe; Somasundaram, Kumaravel

doi:10.7554/elife.78972

Cited by 9 publications

(5 citation statements)

References 81 publications

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“…FMOD led to liver and lung fibrosis by promoting collagen I deposition [ 41 ]. FMOD promoted angiogenesis by downregulating multiple microenvironmental factors including VEGF, TGF-β1, FGF-2, and PDGF-B [ 42 , 43 ]. FMOD upregulation in NFs after low-dose arecoline treatment indicated that arecoline could improve the fiber-forming ability of fibroblasts during OSF pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma

et al. 2023

BMC Oral Health

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Background Betel nut chewing plays a role in the pathogenesis of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC). As the major active ingredient of the betel nut, the effect of arecoline and its underlying mechanism to OSF and OSCC pathogenesis remain unclear. Methods Next-generation sequencing-based transcriptome and dRRBS analysis were performed on OSF and OSCC cells under low-dose arecoline exposure. Functional analyses were performed to compare the different roles of arecoline during OSF and OSCC pathogenesis, and key genes were identified. Results In this study, we identified that low-dose arecoline promoted cell proliferation of both NFs and OSCC cells via the acceleration of cell cycle progression, while high-dose arecoline was cytotoxic to both NFs and OSCC cells. We performed for the first time the transcriptome and methylome landscapes of NFs and OSCC cells under low-dose arecoline exposure. We found distinct transcriptome and methylome profiles mediated by low-dose arecoline in OSF and OSCC cells, as well as specific genes and signaling pathways associated with metabolic disorders induced by low-dose arecoline exposure. Additionally, low-dose arecoline displayed different functions at different stages, participating in the modulation of the extracellular matrix via Wnt signaling in NFs and epigenetic regulation in OSCC cells. After exposure to low-dose arecoline, the node roles of FMOD in NFs and histone gene clusters in OSCC cells were found. Meanwhile, some key methylated genes induced by arecoline were also identified, like PTPRM and FOXD3 in NFs, SALL3 and IRF8 in OSCC cells, indicating early molecular events mediated by arecoline during OSF and OSCC pathogenesis. Conclusions This study elucidated the contribution of low-dose arecoline to OSF and OSCC pathogenesis and identified key molecular events that could be targeted for further functional studies and their potential as biomarkers.

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Section: Discussionmentioning

confidence: 99%

Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma

et al. 2023

BMC Oral Health

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“…found that FMOD promotes glioma angiogenesis and growth by activating integrin-dependent Notch signaling in endothelial cells. 23 Correspondingly, targeting cell surface protein FMOD has been found to be a promising therapeutic approach for triple-negative breast cancer, colorectal cancer melanoma, and chronic lymphocytic leukemia. 24 , 25 , 26 , 27 , 28 Nevertheless, the expression signature, clinical significance, and biological role of FMOD in OSCC remain largely unclear.…”

Section: Discussionmentioning

confidence: 99%

Fibromodulin overexpression drives oral squamous cell carcinoma via activating downstream EGFR signaling

Xia,

Zhang,

Yao

et al. 2023

iScience

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“…Several recent studies have shown, among others, that SLRPs play a greater role during tumorigenesis, particularly tumor epithelial-mesenchymal transition [127,128]. For example, FMOD secreted by differentiated glioma cells (DGCs) promoted angiogenesis by activating integrin dependent Notch signals in endothelial cells [129]. In addition, FMOD and SOX2 signal coupling positively regulated the brain metastasis and growth of melanoma [130].…”

Section: Discussionmentioning

confidence: 99%

Small Leucine Rich Proteoglycan in Fibrotic Diseases: New Frenemies?

Guo

Wang²,

Liang³

et al. 2023

IJDDP

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Review Small Leucine Rich Proteoglycan in Fibrotic Diseases: New Frenemies? Jiayu Guo 1,2, Yan Wang 1,2, Haihai Liang 1,2,3,*, and Baofeng Yang 1,2,3,* 1 Department of Pharmacology (National Key Laboratory of Frigid Zone Cardiovascular Diseases), College of Pharmacy, Harbin Medical University, Harbin 150081, China 2 Northern Translational Medicine Research and Cooperation Center, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin 150081, China 3 Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China * Correspondence: lianghaihai@ems.hrbmu.edu.cn (H.H.L),; yangbf@ems.hrbmu.edu.cn (B.F.Y) Received: 27 April 2023 Accepted: 2 June 2023 Abstract: The human body is a complex organism with self-regulating ability and can cope with external pressures and challenges. To protect the body from damage during exercise or confrontations, beneath the human epidermal layer, the human body has evolved a coverall gown: the extracellular matrix (ECM). ECM provides a suitable space for the survival and activity of cells in the body, and affects the behavior of cells through signal transduction system. Proteoglycans, particularly the small leucine rich proteoglycan (SLRP) family, have been shown to be molecules that play important roles in matrix remodeling and organ fibrosis, such as by affecting ECM components or altering the intracellular environment. But in recent years reports of SLRP families, their manifestations in different organs have not been consistent. Recent studies suggest that proteoglycans entering the blood in a soluble form hold promise as diagnostic biomarkers of organ fibrosis and may provide novel therapeutic strategies for fibrotic diseases. Herein, we discuss and review studies of SLRPs in multi-organ fibrotic diseases.

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Differentiated glioma cell-derived fibromodulin activates integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth

Cited by 9 publications

References 81 publications

Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma

Low-dose arecoline regulates distinct core signaling pathways in oral submucous fibrosis and oral squamous cell carcinoma

Fibromodulin overexpression drives oral squamous cell carcinoma via activating downstream EGFR signaling

Small Leucine Rich Proteoglycan in Fibrotic Diseases: New Frenemies?

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