Membrane potential modulates ERK activity and cell proliferation DOI Open Access
Mari Sasaki,

M. Nakahara,

T. Hashiguchi

et al.

Published: Oct. 22, 2024

The plasma membrane potential has been linked to cell proliferation for more than 40 years. Here we experimentally showed that depolarization upregulates mitosis, and this process is dependent on voltage-dependent activation of ERK. ERK activity exhibits a potential-dependency independent from the growth factor. This dependence was observed even close resting potential, indicating small changes in can alter proliferative activity. derived changed dynamics phosphatidylserine which present not by extracellular calcium entry. data suggests crucial biological processes such as are regulated physicochemical properties lipid. study may have diverse physiological functions beyond action well-established neural system.

Language: Английский

Compressive stresses in cancer: characterization and implications for tumour progression and treatment DOI

Julia A Linke,

Lance L. Munn, Rakesh K. Jain

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(11), P. 768 - 791

Published: Oct. 10, 2024

Language: Английский

Citations

11

ERK activation waves coordinate mechanical cell competition leading to collective elimination via extrusion of bacterially infected cells DOI Creative Commons
Lara Hundsdorfer, Marie Muenkel, Raúl Aparicio-Yuste

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115193 - 115193

Published: Jan. 1, 2025

Epithelial cells respond to infection with the intracellular bacterial pathogen Listeria monocytogenes by altering their mechanics promote collective infected cell extrusion (CICE) and limit spread across monolayers. However, underlying biochemical pathways remain elusive. Here, using in vitro (epithelial monolayers) vivo (zebrafish larvae) models of L. or Shigella flexneri, we explored role extracellular-signal-regulated kinase (ERK) activity waves coordinating mechanical battle between surrounder uninfected that leads CICE. We discovered when ERK are suppressed, fail exhibit alterations shape kinematics associated CICE behave more like quiescent In particular, surrounding foci unable polarize, reinforce monolayer stresses, Our findings reveal crosstalk is key elimination large domains cells.

Language: Английский

Citations

1

Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification DOI Creative Commons
Matea Brezak, Zuzana Koledová

Journal of Mammary Gland Biology and Neoplasia, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 18, 2025

Language: Английский

Citations

1

Tumor dormancy and relapse: understanding the molecular mechanisms of cancer recurrence DOI Creative Commons
Muhammad Tufail, Canhua Jiang, Ning Li

et al.

Military Medical Research, Journal Year: 2025, Volume and Issue: 12(1)

Published: Feb. 11, 2025

Abstract Cancer recurrence, driven by the phenomenon of tumor dormancy, presents a formidable challenge in oncology. Dormant cancer cells have ability to evade detection and treatment, leading relapse. This review emphasizes urgent need comprehend dormancy its implications for recurrence. Despite notable advancements, significant gaps remain our understanding mechanisms underlying lack reliable biomarkers predicting provides comprehensive analysis cellular, angiogenic, immunological aspects dormancy. It highlights current therapeutic strategies targeting dormant cells, particularly combination therapies immunotherapies, which hold promise preventing By elucidating these proposing innovative research methodologies, this aims deepen ultimately facilitating development more effective recurrence improving patient outcomes.

Language: Английский

Citations

1

MEK inhibitors: a promising targeted therapy for cardiovascular disease DOI Creative Commons

Khaled Abdelsattar Kassem Mohammed,

Paolo Madeddu, Elisa Avolio

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: July 1, 2024

Cardiovascular disease (CVD) represents the leading cause of mortality and disability all over world. Identifying new targeted therapeutic approaches has become a priority biomedical research to improve patient outcomes quality life. The RAS-RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathway is gaining growing interest as potential signaling cascade implicated in pathogenesis CVD. This pivotal regulating cellular processes like proliferation, growth, migration, differentiation, survival, which are vital maintaining cardiovascular homeostasis. In addition, ERK involved controlling angiogenesis, vascular tone, myocardial contractility, oxidative stress. Dysregulation this been linked cell dysfunction cardiac pathological remodeling, contribute onset progression Recent ongoing provided insights into interventions targeting RAS-RAF-MEK-ERK pathologies. Preclinical studies have demonstrated efficacy therapy with MEK inhibitors (MEKI) attenuating activation mitigating CVD animal models. article, we first describe how contributes preserving health. We then summarize current knowledge roles played by development disorders, including atherosclerosis, infarction, hypertrophy, heart failure, aortic aneurysm. finally report novel strategies for these CVDs encompassing MEKI discuss advantages, challenges, future developments therapeutics.

Language: Английский

Citations

4

Bud, Branch, Breathe! Building a mammalian lung over space and time DOI Creative Commons
Brigid L.M. Hogan

Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Many mammalian organs, such as the mammary and lachrymal glands, kidney lungs develop by process known branching morphogenesis. An essential feature of this is reciprocal interaction between inner branched tubular epithelium surrounding mesenchyme to optimize final amount epithelial tissue that generated for specific functions. To achieve expansion initial population undergoes repeated rounds bud formation, branch outgrowth tip bifurcations, with each repertoire requiring dynamic changes in cell behavior. The morphogenesis was first studied experimentally Grobstein others who showed embryonic did not without so-called inductive signals from mesenchyme. However, it whether activity uniformly distributed throughout mesoderm or localized regions. mouse lung seen a powerful system which investigate questions since its early highly stereotypic, both vivo culture. This advantage exploited two young scientists, Alescio Cassini, used grafting techniques explanted lungs. They around distal buds could induce ectopic trachea other non-branching regions epithelium. At same time, denuded their failed further. speculated factors promote formation continued competent endoderm are specifically within mesenchyme, establishing conceptual framework future experimentation. Since then, advances many areas biology bioengineering have enabled identification gene regulatory networks, signaling pathways biomechanical properties mediate quantitative model how these parameters coordinated over space time control pattern scale overall size lung, still remains elusive.

Language: Английский

Citations

0

Gossiping about death: Apoptosis-induced ERK waves as coordinators of multicellular fate decisions DOI Creative Commons
Paolo Armando Gagliardi, Olivier Pertz

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 171, P. 103615 - 103615

Published: April 24, 2025

Apoptosis is now recognized as a highly dynamic process that involves the release of large set signaling molecules convey information to cells neighboring an apoptotic site. Recent studies in epithelial systems have discovered trigger waves pulses mitogen-activated protein kinase (MAPK) / extracellular signal-regulated (ERK) pathway activity their neighbors. At single-cell level, ERK emerge from MAPK pathway's excitable network properties, such ultrasensitivity and adaptation. cell population apoptosis-induced (AiEWs) propagation across via mechanism mechanical inputs paracrine signaling. AiEWs enable populations dynamically coordinate fate decision during tissue homeostasis development. This spatio-temporal can be hijacked by cancer induce drug-tolerant persister states when apoptosis triggered cytotoxic or targeted therapies, undermining treatment efficacy. In this review, we summarize our current understanding AiEWs, including initiation, propagation, coordination within population. We discuss how relatively simple properties single cells, interactions collective these patterns. highlight implication resistance therapy explore potential strategies target re-sensitize cells. Finally, emerging technologies future directions expand study biological phenomenon.

Language: Английский

Citations

0

3D Mechanical Response Stem Cell Complex Repairs Spinal Cord Injury by Promoting Neurogenesis and Regulating Tissue Homeostasis DOI Open Access
Jingwei Jiu, Haifeng Liu,

Dijun Li

et al.

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

Published: Jan. 24, 2025

Abstract Spinal cord injury (SCI) leads to acute tissue damage that disrupts the microenvironmental homeostasis of spinal cord, inhibiting cell survival and function, thereby undermining treatment efficacy. Traditional stem therapies have limited success in SCI, due difficulties maintaining inducing sustained differentiation into neural lineages. A new solution may arise from controlling fate cells by creating an appropriate mechanical microenvironment. In this study, response complex (MRSCC) is created as innovative therapeutic strategy for utilizing 3D bioprinting technology gelatin microcarriers (GM) loaded with mesenchymal (MSCs). GM creates optimal microenvironment MSCs growth paracrine activity. Meanwhile, allows accurate control spatial pore architecture characteristics construct encourage neuroregeneration. The MRSCC found activate Piezo1 channel prevent excessive nuclear translocation YAP, increasing neural‐related gene expression MSCs. Transplanting rats injuries boosts sensory motor recovery, reduces inflammation, stimulates regeneration neurons glial cells. offers a engineering can promote repair.

Language: Английский

Citations

0

Harnessing the power of physicochemical material property screening to direct breast epithelial and breast cancer cells DOI
Lisa E. Tromp,

R. de Josselin de Jong,

Torben A. B. van der Boon

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 50, P. 494 - 509

Published: April 26, 2025

Language: Английский

Citations

0

Nuclear envelope proteins, mechanotransduction, and their contribution to breast cancer progression DOI Creative Commons

Sarah Henretta,

Jan Lammerding

npj Biological Physics and Mechanics., Journal Year: 2025, Volume and Issue: 2(1)

Published: May 5, 2025

Breast cancer cells frequently exhibit changes in the expression of nuclear envelope (NE) proteins such as lamins and emerin that determine physical properties nucleus contribute to cellular mechanotransduction. This review explores emerging interplay between NE proteins, challenges incurred during metastatic progression, Improved insights into underlying mechanisms may ultimately lead better prognostic tools treatment strategies for breast cancer.

Language: Английский

Citations

0