ETS-1 in tumor immunology: implications for novel anti-cancer strategies

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 20, 2025

ETS-1, a key member of the Erythroblast Transformation-Specific (ETS) transcription factor family, plays an important role in cell biology and medical research due to its wide expression profile strong transcriptional regulation ability. It regulates fundamental biological processes, including proliferation, differentiation, apoptosis, is involved tumorigenesis metastasis, promoting malignant behaviors such as angiogenesis, matrix degradation, migration. Given association between ETS-1 overexpression aggressive characteristics multiple malignancies, it represents promising therapeutic target cancer treatment. This study aims systematically analyze within tumor immune microenvironment, elucidating mechanisms initiation, progression, metastasis. also investigates differential across tissues adjacent normal tissues, exploring potential molecular marker for diagnosis prognosis.

Language: Английский

BDNF controls phosphorylation and transcriptional networks governing cytoskeleton organization and axonal regeneration

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 6, 2023

SUMMARY Axonal degeneration underlies neuromuscular disorders and neuropathies. Dysregulation of neurotrophic factors, such as brain-derived factor (BDNF), in the peripheral nervous system has long been established to exacerbate axonopathy. However, molecular programs controlled by BDNF that facilitate axonal regeneration transport are not well-understood. Here, we unravel transcriptomic phosphorylation landscape shaped human iPSC-derived motor neurons. Using SLAM-Seq, reveal stimulation increases global transcription rate neurons governs gene regulatory networks converge with those engaged during repair/outgrowth. Phosphoproteomic analyses demonstrate remodels cytoskeletal-binding proteins, especially structural microtubule-associated proteins. Importantly, localized axonal-specific activation ERK1/2 is necessary for enhance neurotrophin-containing signaling endosomes potentiate after axotomy. Collectively, this work unveils a novel paradigm positions core regulator transcriptional driving HIGHLIGHTS SLAM-seq reveals increased modulates outgrowth/regeneration proteins BDNF-ERK1/2 controls

Language: Английский

Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 17, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons (MNs), which innervate skeletal muscles. However, certain MN groups including ocular MNs that regulate eye movement are relatively resilient to ALS. To reveal mechanisms differential susceptibility, we investigate transcriptional dynamics two vulnerable and populations in SOD1G93A ALS mice. Analysis differentially expressed genes (DEGs) shows each neuron type displays a largely unique spatial temporal response disease. Baseline gene expression clearly divergent from their mutant SOD1 minor, with regulation few genes, some known neuroprotective properties, e.g. Ucn , Cck Postn . EASE, fGSEA ANUBIX enrichment analysis demonstrate share pathway activation, neuronal death, inflammatory response, ERK MAPK cascades, cell adhesion synaptic signaling. These pathways driven 11 upregulated Atf3, Nupr1, Cd44, Gadd45a, Ngfr, Ccl2, Ccl7, Gal, Timp1, Serpinb1a Chl1 indicate death occurs through similar across albeit distinct timing. Machine learning using DEGs our spinal predict disease human stem cell-derived harboring SOD1E100G mutation, show dysregulation VGF INA, PENK NTS strong disease-predictors mutations species. Meta-analysis transcriptome datasets identifies shared vulnerability code 32 e.g Atf3 Nupr1 Vgf Ina Sprr1a, Fgf21, C1qb, Gap43, Adcyap1, Mt1 In conclusion study reveals cell-type-specific dynamic disease-induced may act preserve can be used

Language: Английский