Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix DOI Creative Commons

Máté Lengyel,

Ádám Molnár,

Tamás Milán Nagy

et al.

Cancer Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Abstract High tissue density of the mammary gland is considered a pro‐tumorigenic factor, hence suppressing stimuli that induce matrix buildup carries potential for cancer interception. We found in non‐malignant epithelial cells combination chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses zymogen granule protein 16B (ZG16B, PAUF) through an interaction ARID1A with proximal enhancer. Bex + Carv also reduced ZG16B levels vivo normal breast MDA‐MB231 tumor xenografts. The relevance underscored by ongoing clinical trials targeting pancreatic cancers, but its role development unclear. In immortalized cells, secreted recombinant stimulated mitogenic kinase phosphorylation, detachment mesenchymal characteristics, promoted proliferation, motility clonogenic growth. Highly concerted induction specific laminin, collagen integrin isoforms indicated shift properties toward increased cell‐matrix interactions. Exogenous alone blocked Carv‐mediated control cell growth migration, antagonized Carv‐induced gene programs regulating adhesion migration. induced colony formation anchorage‐independent growth, migration PI3K/Akt‐dependent manner. contrast, inhibited formation, Ki67 levels, expression glucose uptake These data establish as druggable target transformation suggest key matrisome network rexinoid‐dependent antitumor activity.

Language: Английский

Feeling the force from within – new tools and insights into nuclear mechanotransduction DOI Creative Commons
Julien Morival,

Anna Hazelwood,

Jan Lammerding

et al.

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(5)

Published: March 1, 2025

The ability of cells to sense and respond mechanical signals is essential for many biological processes that form the basis cell identity, tissue development maintenance. This process, known as mechanotransduction, involves crucial feedback between force biochemical signals, including epigenomic modifications establish transcriptional programs. These programs, in turn, reinforce properties its withstand perturbation. nucleus has long been hypothesized play a key role mechanotransduction due direct exposure forces transmitted through cytoskeleton, receiving cytoplasmic central function gene regulation. However, parsing out specific contributions from those surface cytoplasm remains substantial challenge. In this Review, we examine latest evidence on how regulates both via nuclear envelope (NE) epigenetic machinery elements within interior. We also explore establishing memory, characterized by mechanical, transcriptomic state persists after stimuli cease. Finally, discuss current challenges field present technological advances are poised overcome them.

Language: Английский

Citations

1
Regulation and mechanistic insights into tensile strain in mesenchymal stem cell osteogenic differentiation DOI
Yongxin Zhang, Feng Xu, Bowen Zheng

et al.

Bone, Journal Year: 2024, Volume and Issue: 187, P. 117197 - 117197

Published: Oct. 1, 2024

Language: Английский

Citations

4
Development and Characterization of Three Novel FGFR Inhibitor Resistant Cervical Cancer Cell Lines to Help Drive Cervical Cancer Research DOI Open Access

Nauf Bou Antoun,

Hiba-Tun-Noor A. Mahmood,

Anthony J. Walker

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1799 - 1799

Published: Feb. 20, 2025

Primary or acquired resistance to therapeutic agents is a major obstacle in the treatment of cancer patients. Cervical fourth leading cause deaths among women worldwide and, despite advances screening and treatments, many patients with advanced stage cervical have high recurrence rate within two years standard treatment, drug being contributing factor. The development cell lines can facilitate comprehensive investigation mechanisms, which cannot be easily performed clinical trials. This study aimed create three novel robust (HeLa, CaSki, SiHa) fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor (PD173074). All drug-resistant (DR) overexpressed FGFR1, FGFR2, FGF2, FGF4, FGF7 proteins that were also localized nucleus. In addition, DR cells had significantly more aggressive phenotype (more migratory proliferative, less apoptotic) compared parental lines. These are critical tool for understanding molecular mechanisms underpinning identification potential biomarkers. Moreover, availability such may effective strategies using FGFR inhibitors combination other target pathways responsible inhibitors.

Language: Английский

Citations

0
Mechanical Forces, Nucleus, Chromosomes, and Chromatin DOI Creative Commons
M. Kloc, J. Wosik

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 354 - 354

Published: March 1, 2025

Individual cells and within the tissues organs constantly face mechanical challenges, such as tension, compression, strain, shear stress, rigidity of cellular extracellular surroundings. Besides external forces, their components are also subjected to intracellular pulling, pushing, stretching, created by sophisticated force-generation machinery cytoskeleton molecular motors. All these stressors switch on mechanotransduction pathways, allowing respond adapt. Mechanical force-induced changes at cell membrane transmitted nucleus its nucleoskeleton, affecting nucleocytoplasmic transport, chromatin conformation, transcriptional activity, replication, genome, which, in turn, orchestrate behavior. The memory mechanoresponses is stored epigenetic structure modifications. state response acellular environment determines identity, fate, immune invading pathogens. Here, we give a short overview latest developments understanding processes, emphasizing effects nuclei, chromosomes, chromatin.

Language: Английский

Citations

0
Molecular mechanisms in regulation of autophagy and apoptosis in view of epigenetic regulation of genes and involvement of liquid-liquid phase separation DOI

Subhajit Chakraborty,

Piyasa Nandi,

Jagdish Mishra

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216779 - 216779

Published: March 6, 2024

Language: Английский

Citations

3
Dissecting SOX2 expression and function reveals an association with multiple signaling pathways during embryonic development and in cancer progression DOI

Niharika Niharika,

Lina Ureka,

Ankan Roy

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(5), P. 189136 - 189136

Published: June 15, 2024

Language: Английский

Citations

3
Mechanotransduction Circuits in Human Pathobiology DOI Open Access
Antonios N. Gargalionis, Kostas A. Papavassiliou, Athanasios G. Papavassiliou

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3816 - 3816

Published: March 29, 2024

It is widely acknowledged that mechanical forces exerted throughout the human body are critical for cellular and tissue homeostasis [...].

Language: Английский

Citations

1
Structure-Mechanics Principles and Mechanobiology of Fibrocartilage Pericellular Matrix: A Pivotal Role of Type V Collagen DOI
Chao Wang, Mingyue Fan,

Su-Jin Heo

et al.

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

Published: June 30, 2024

The pericellular matrix (PCM) is the immediate microniche surrounding resident cells in various tissue types, regulating turnover, cell-matrix cross-talk and disease initiation. This study elucidated structure-mechanical properties mechanobiological functions of PCM fibrocartilage, a family connective tissues that sustain complex tensile compressive loads vivo. Studying murine meniscus as model tissue, we showed fibrocartilage contains thinner, random collagen fibrillar networks entrap proteoglycans, structure distinct from densely packed, highly aligned fibers bulk extracellular (ECM). In comparison to ECM, has lower modulus greater isotropy, but similar relative viscoelastic properties.

Language: Английский

Citations

0
Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix DOI Creative Commons

Máté Lengyel,

Ádám Molnár,

Tamás Milán Nagy

et al.

Cancer Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Abstract High tissue density of the mammary gland is considered a pro‐tumorigenic factor, hence suppressing stimuli that induce matrix buildup carries potential for cancer interception. We found in non‐malignant epithelial cells combination chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses zymogen granule protein 16B (ZG16B, PAUF) through an interaction ARID1A with proximal enhancer. Bex + Carv also reduced ZG16B levels vivo normal breast MDA‐MB231 tumor xenografts. The relevance underscored by ongoing clinical trials targeting pancreatic cancers, but its role development unclear. In immortalized cells, secreted recombinant stimulated mitogenic kinase phosphorylation, detachment mesenchymal characteristics, promoted proliferation, motility clonogenic growth. Highly concerted induction specific laminin, collagen integrin isoforms indicated shift properties toward increased cell‐matrix interactions. Exogenous alone blocked Carv‐mediated control cell growth migration, antagonized Carv‐induced gene programs regulating adhesion migration. induced colony formation anchorage‐independent growth, migration PI3K/Akt‐dependent manner. contrast, inhibited formation, Ki67 levels, expression glucose uptake These data establish as druggable target transformation suggest key matrisome network rexinoid‐dependent antitumor activity.

Language: Английский

Citations

0