Suppression of Spry1 reduces HIF1α-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 14, 2025

About 50% of cutaneous melanoma (CM) harbors the activating BRAFV600 mutation which exerts most oncogenic effects through MAPK signaling pathway. In last years, a number modulators have been identified, including Spry1. this context, we recently demonstrated that knockout Spry1 (Spry1KO) in BRAFV600-mutant CM led to cell cycle arrest and apoptosis, repressed proliferation vitro, reduced tumor growth vivo. Despite these findings, however, precise molecular mechanism linking remains be elucidated. Immunoprecipitation coupled mass spectrometry was employed gain insight into interactome. gene knocked-out using CRISPR strategy BRAF-mutant lines. Transmission electron microscopy used assess relationship between expression mitochondrial morphology. By vitro vivo models, Spry1KO were investigated RNA-sequencing, quantitative real-time PCR, Western blot, immunofluorescence analyses. The Seahorse XF24 assay allowed measurement cellular metabolism our model. Angiogenic potential assessed tube formation assays CD31 staining. mainly located mitochondria cells where it interacted with key molecules involved homeostasis. loss resulted shape alterations dysfunction, associated increased reactive oxygen species production. agreement, found nuclear hypoxia-inducible factor-1 alpha (HIF1α) protein levels clones both along its glycolysis related genes. Accordingly, Ingenuity Pathway Analysis identified "HIF1α Signaling" as significant function affected by silencing, whereas glycolytic significantly impaired depleted cells. addition, results indicated vascular endothelial factor A down-regulated following Spry1KO, possibly result dysfunction. Consistently, observed substantial impairment angiogenesis, staining Altogether, findings identify regulator homeostasis, uncover previously unrecognized role for regulating HIF1α angiogenesis CM. profoundly impacts on while concomitantly impairing HIF1α-dependent reducing cells, thus providing therapeutic target improve treatment.

Language: Английский

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New indolin-2-ones, possessing sunitinib scaffold as HDAC inhibitors and anti-cancer agents with potential VEGFR inhibition activity; design, synthesis and biological evaluation

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 156, P. 108231 - 108231

Published: Jan. 30, 2025

Language: Английский

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Functionalized Cerium Oxide Nanoparticles Enhance Penetration into Melanoma Spheroids In Vivo through Angiogenesis

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Abstract Angiogenesis is a crucial step in tumor progression, including melanoma, making anti‐angiogenic strategies widely explored treatment approach. However, both innate and acquired resistance to these therapies suggest that this approach may need re‐evaluation. Nanoparticles have gained attention for their potential enhance drug delivery retention within tumors via the bloodstream. vitro screening of nanoparticles limited by inability preclinical models replicate complex microenvironment, especially blood supply. Here, it demonstrated melanoma cells embedded Matrigel spheroids can engraft be vascularized chorioallantoic membrane (CAM) fertilized chicken eggs. This model allows assessment nanoparticle toxicity accumulation spheroids, as well functional effects such angiogenesis. Cerium oxide (nanoceria) surface functionalized derivatives are biomedical applications due ability modulate oxidative stress observed heparin nanoceria penetrate CAM promote spheroid vascularization greater extent than alone. study aids development cancer provides new insight into interplay between coatings biological effects.

Language: Английский

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Breast cancer-derived CAV1 promotes lung metastasis by regulating integrin α6β4 and the recruitment and polarization of tumor-associated neutrophils

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(14), P. 5695 - 5714

Published: Oct. 14, 2024

Lung metastasis in breast cancer (BC) patients is one of the main reasons for their high mortality rate. The most prevalent BC small extracellular vesicles (sEVs receptor, integrin α6β4, has been found to interact with surfactant-associated protein (SFTPC) lung epithelial cells, making more likely metastasize lung. Tumor-associated neutrophils (TANs) play an essential role as a component pre-metastatic niche (PMN) two sides. It demonstrated that Toll-like Receptor4 (TLR4) can participate signaling, such NF-B and NLRP3, facilitate tumor metastasis. A cellular membrane structural called caveolin-1 (CAV1) associated BC's proliferation, metastasis, immunological control. According our previous research, CAV1 on BC-derived sEVs facilitates formation PMN by enhancing tenascin-C (TnC) secretion fibroblasts promote deposition ECM, increasing expression marker genes inflammatory chemokines supporting N2-type polarization macrophages via inhibiting PTEN/CCL2/VEGF-A axis. More research needed determine how sEVs-mediated BC-targeted lungs. By creating stable-translocating cell line stably interfered mouse model we investigated promotes TAN recruitment

Language: Английский

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Introduction to Neoplasia

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Innate Immunity and Angiogenesis

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Deficiency of myeloid discoidin domain receptor 2 aggravates melanoma lung and bone metastasis

Investigational New Drugs, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

Language: Английский

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