Brain Plasticity and Cell Competition: Immediate Early Genes Are the Focus

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 143 - 143

Published: Jan. 19, 2025

Brain plasticity is at the basis of many cognitive functions, including learning and memory. It includes several mechanisms synaptic extrasynaptic changes, neurogenesis, formation elimination synapses. The transmission involves expression immediate early genes (IEGs) that regulate neuronal activity, thereby supporting In addition, IEGs are involved in regulation brain cells’ metabolism, proliferation, survival, establishment multicellular ensembles, and, presumably, cell competition tissue. this review, we analyze current understanding role (c-Fos, c-Myc, Arg3.1/Arc) controlling physiological pathological conditions, aging neurodegeneration. This work might inspire new gene therapy strategies targeting to plasticity, potentially prevent or mitigate neurodegenerative diseases.

Language: Английский

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Electrical Stimulation Generates Induced Tumor-Suppressing Cells, Offering a Potential Option for Combatting Breast Cancer and Bone Metastasis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1030 - 1030

Published: Jan. 25, 2025

Treating advanced metastatic cancer, particularly with bone metastasis, remains a significant challenge. In previous studies, induced tumor-suppressing (iTS) cells were successfully generated through genetic, chemical, and mechanical interventions. This study investigates the potential of electrical stimulation to generate iTS cells. Using custom stimulator platinum electrodes, mesenchymal stem (MSCs) Jurkat T stimulated under optimized conditions (50 mV/cm, 10–100 Hz, 1 h). Conditioned medium (CM) from electrically demonstrated capabilities, inhibiting tumor cell migration, 3D spheroid growth, cancer tissue fragment viability. Additionally, CM reduced osteoclast maturation while promoting osteoblast differentiation. Proteomic analysis revealed enrichment proteins, including histone H4, in CM. Functional studies identified Piezo1 as key mediator, its knockdown significantly impaired tumor-suppressive effects. Mechanistically, process was distinct other methods, such vibration, SUN1 inhibition showing no effect on generation by stimulation. These findings demonstrate efficacy enhancing antitumor capabilities MSCs cells, offering novel approach therapy. Further exploration this strategy could provide valuable insights into developing new treatments for cancer.

Language: Английский

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Functions of Drosophila Toll/NF-κB signaling in imaginal tissue homeostasis and cancer

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 12, 2025

The Toll/NF-κB pathway plays a central role in patterning the Drosophila embryo and orchestrating innate immune response against microbial infections. Both discoveries were associated with Nobel Prize award led to recognition of Toll-like receptor mammals, which has significant implications for diseases. Recent have revealed that also maintains epithelial homeostasis imaginal tissues during development: local signaling activity monitors internal cellular fitness, precancerous mutant cells can trigger systemic activation. However, this be exploited diseases like cancer, is often co-opted or subverted. Various models been proposed explain how contributes different types cancer. Here we provide an overview functions tissue focus on their misuse pathological contexts, particularly significance tumor formation.

Language: Английский

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Actin cytoskeletal deregulation, caused by RhoGEF2 overexpression, induces cell competition dependent on Ptp10D, Crumbs, and the Hippo signaling pathway.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Abstract In Drosophila larval epithelial tissues, cells containing mutations in the apico-basal polarity proteins, Scrib, Dlg or Lgl, are eliminated by cell competition when surrounded wild-type cells. these polarity-impaired cells, signaling mediated receptor-type tyrosine phosphatase Ptp10D upon engagement with its ligand Sas surrounding triggers via EGFR pathway inhibition and JNK activation, which induces apoptosis of mutant Here, we investigate whether directly triggering cytoskeletal deregulation (which usually occurs downstream disruptions) is sufficient to trigger their elimination Sas-Ptp10D system. We show that actin cytoskeleton deregulated (as induced RhoGEF2 overexpression ( OE )) knockdown increases clone growth, revealing importance Mechanistically, clones moderately overexpressing , rescued reducing Hippo signaling. this setting, EGFR-Ras were not affected (in contrast what cells), suggesting may regulate also found apical protein, Crb, partially clones, showing Crb normally plays a role elimination. highly overexpressed, elevated while was reduced, crb loss normalized pathways. showed reduced abundance membrane localization Ptp10D, play an important competition. Thus, deregulation, caused results dependent on Altogether, our reveal acting more broadly loser as well

Language: Английский

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The Initiator Caspase Dronc Drives Compensatory Proliferation of Apoptosis-Resistant Cells During Epithelial Tissue Regeneration After Ionizing Radiation

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

Published: Sept. 2, 2024

Abstract Caspases, well-known for their role in executing apoptosis, also participate various non-apoptotic processes. Despite this, involvement promoting compensatory proliferation - a key aspect of tissue regeneration following extensive cell death has been subject ongoing ambiguity. In our study, we investigate the Drosophila wing imaginal disc ionizing radiation, model epithelial that pioneering system studying this regenerative response. Using delayed genetic reporter to monitor activity initiator caspase-2/9 ortholog, Dronc, identified two populations apoptosis-resistant cells involved proliferation: those activate Dronc (termed DARE cells) and do not (NARE cells). We show pass apoptosis-resistance trait daughter cells, suggesting molecular memory. demonstrate but apoptosome adapter Dark effector caspases, promotes both within these NARE through non-cell-autonomous mechanism. found Myo1D, an unconventional myosin interacting with is essential survival by preventing lethal activation caspases subsequent apoptosis. contrast, Myo7A/Crinkled, another interacts caspase cells. TNFR>JNK signaling pathway directly regulates proliferation, which turn influences proliferation. Consequently, maintaining proliferative homeostasis between vital balanced regeneration. Given widespread use irradiation cancer treatment prevention, findings have potential implications understanding treatment-resistant recurrence.

Language: Английский

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Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis

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

Published: Oct. 26, 2024

Abstract Toys are us (Trus) is the Drosophila melanogaster ortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined function Trus during development. CRISPR/Cas9 generated null mutations trus lead to partial embryonic lethality, significant larval developmental delay, complete pre-pupal lethality. mutant larvae, found decreased proliferation growth defects brain imaginal discs. Mapping relevant tissues for using RNAi rescue experiments revealed disc primarily responsible while lethality likely associated with faulty central nervous system (CNS) Examination molecular mechanism behind delay phenotype induce Xrp1-Dilp8 ribosomal stress-response growth-impaired discs, signaling pathway attenuates production hormone ecdysone prothoracic gland. Additional Tap-tagging mass spectrometry components complexes isolated from Kc cells identified Ribosomal subunit 2 (RpS2), which coded by string pearls (sop) Drosophila, Eukaryotic translation elongation factor 1 alpha (eEF1α1) as interacting factors. We discuss implication these findings respect similarity differences genetic phenotypes compared haplo-insufficiency produced heterozygosity mutants Minute genes other involved biogenesis. Authors Summary Ribosomes essential macromolecular machines required decoding mRNA make proteins, major biomolecules carry out all cellular functions. As such, their structural operational integrity critical organismal survival, disrupt proper stoichiometry or assembly ribosomes produce serious pathological consequences an organism’s development and/or adult life. The PDCD2L highly conserved yeast man, yet its overall requirement poorly understood. By examining , encodes homolog, demonstrate role cell-cycle regulation. Furthermore, disruption mitotically dividing tissue activates Xrp1-dilp8 stress response limits ecdysone, arthropod molting hormone, leading severe stages. These studies provide new insights on requirements assemble

Language: Английский

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Autocrine Motility Factor and Its Peptide Derivative Inhibit Triple-Negative Breast Cancer by Regulating Wound Repair, Survival, and Drug Efflux

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11714 - 11714

Published: Oct. 31, 2024

Triple-negative breast cancer (TNBC) presents a significant challenge in oncology due to its aggressive nature and limited targeted therapeutic options. This study explores the potential of autocrine motility factor (AMF) an AMF-derived peptide as novel treatments for TNBC. AMF, primarily secreted by neoplastic cells, plays crucial role cell motility, metastasis, proliferation. The research demonstrates that AMF derived inhibit TNBC proliferation modulating cellular migration, redox homeostasis, apoptotic pathways, drug efflux mechanisms. Dose-dependent antiproliferative effects were observed across three lines, with higher concentrations impairing migration. Mechanistic studies revealed decreased glucose-6-phosphate dehydrogenase expression elevated reactive oxygen species production, suggesting imbalance primary mediator apoptosis. Combination conventional therapeutics showed near-complete eradication resistant cells. reduction p53 levels increased intranuclear doxorubicin accumulation highlight AMF/AMF peptide's multidrug resistance modulators. underscores promise using approach TNBC, addressing current treatment limitations warranting further investigation.

Language: Английский

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