Many Ways to the Cell Cycle Exit after Inhibition of CDK4/6 DOI Open Access
Libor Macůrek

Folia Biologica, Год журнала: 2023, Номер 69(5-6), С. 194 - 196

Опубликована: Янв. 1, 2023

Cyclin-dependent kinases (CDKs) are master regulators of proliferation, and therefore they represent attractive targets for cancer therapy. Deve­lopment selective CDK4/6 inhibitors including palbociclib revolutionized the treatment advanced HR + /HER2 – breast cancer. Inhibition leads to cell cycle arrest in G0/G1 phase eventually a permanent exit called senescence. One main features senescence is an increased size. For many years, it was believed that non-dividing cells simply continue grow as result, become excessively large. There now emerging evidence size cause rather than consequence arrest. This review aims summarize recent advances our understanding induction, particular resulting from with inhibitors.

Язык: Английский

Genome homeostasis defects drive enlarged cells into senescence DOI Creative Commons
Sandhya Manohar, Marianna E. Estrada, Federico Uliana

и другие.

Molecular Cell, Год журнала: 2023, Номер 83(22), С. 4032 - 4046.e6

Опубликована: Ноя. 1, 2023

Cellular senescence refers to an irreversible state of cell-cycle arrest and plays important roles in aging cancer biology. Because is associated with increased cell size, we used reversible arrests combined growth rate modulation study how excessive affects proliferation. We find that enlarged cells upregulate p21, which limits progression. Cells re-enter the cycle encounter replication stress well tolerated physiologically sized but causes severe DNA damage cells, ultimately resulting mitotic failure permanent withdrawal. demonstrate fail recruit 53BP1 other non-homologous end joining (NHEJ) machinery sites robustly initiate damage-dependent p53 signaling, rendering them highly sensitive genotoxic stress. propose impaired response primes for persistent replication-acquired damage, leading division exit.

Язык: Английский

Процитировано

38
The intensities of canonical senescence biomarkers integrate the duration of cell-cycle withdrawal DOI Creative Commons
Humza M. Ashraf,

Brianna Fernandez,

Sabrina L. Spencer

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 27, 2023

Abstract Senescence, a state of irreversible cell-cycle withdrawal, is difficult to distinguish from quiescence, reversible withdrawal. This difficulty arises because quiescent and senescent cells are defined by overlapping biomarkers, raising the question whether these states truly distinct. To address this, we use single-cell time-lapse imaging slow-cycling that spend long periods in quiescence never cycle after recovery senescence-inducing treatments, followed staining for various senescence biomarkers. We find intensity multiple biomarkers graded rather than binary reflects duration per se. Together, our data show apparent nearly molecularly indistinguishable each other at snapshot time. suggests withdrawal itself binary, where intensities integrate past

Язык: Английский

Процитировано

29
Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells DOI
Michael C. Lanz, Shuyuan Zhang, Matthew P. Swaffer

и другие.

Nature Structural & Molecular Biology, Год журнала: 2024, Номер unknown

Опубликована: Июль 24, 2024

Язык: Английский

Процитировано

9
Untangling immune cell contributions in the progression from GERD to Barrett’s esophagus and esophageal cancer: Insights from genetic causal analysis DOI
Tai Zhang, Xudong Tang

International Immunopharmacology, Год журнала: 2025, Номер 150, С. 114271 - 114271

Опубликована: Фев. 17, 2025

Язык: Английский

Процитировано

1
Cell Size Contributes to Single-Cell Proteome Variation DOI
Michael C. Lanz, Lucas Fuentes Valenzuela, Joshua E. Elias

и другие.

Journal of Proteome Research, Год журнала: 2023, Номер 22(12), С. 3773 - 3779

Опубликована: Ноя. 1, 2023

Accurate measurements of the molecular composition single cells will be necessary for understanding relationship between gene expression and function in diverse cell types. One most important phenotypes that differs is their size, which was recently shown to an determinant proteome populations similarly sized cells. We, therefore, sought test if effects size on protein concentrations were also evident single-cell proteomics data. Using relative a set reference proteins estimate cell's DNA-to-cell volume ratio, we found differences explain significant amount cell-to-cell variance two published data sets.

Язык: Английский

Процитировано

16
Eukaryotic cell size regulation and its implications for cellular function and dysfunction DOI
Yagya Chadha, Arohi Khurana, Kurt M. Schmoller

и другие.

Physiological Reviews, Год журнала: 2024, Номер 104(4), С. 1679 - 1717

Опубликована: Июнь 20, 2024

Depending on cell type, environmental inputs, and disease, the cells in human body can have widely different sizes. In recent years, it has become clear that size is a major regulator of function. However, we are only beginning to understand how optimization function determines given cell’s optimal size. Here, review currently known control strategies eukaryotic intricate link intracellular biomolecular scaling, organelle homeostasis, cycle progression. We detail size-dependent regulation early development impact differentiation. Given importance for normal cellular physiology, must account changing conditions. describe sense stimuli, such as nutrient availability, accordingly adapt their by regulating growth Moreover, discuss correlation pathological states with misregulation long time this was considered downstream consequence dysfunction. newer studies reveal reversed causality, misregulated leading pathophysiological phenotypes senescence aging. summary, highlight important roles dysfunction, which could implications both diagnostics treatment clinic.

Язык: Английский

Процитировано

6
The environmental stress response regulates ribosome content in cell cycle-arrested S. cerevisiae DOI Creative Commons

Allegra Terhorst,

Arzu Sandikci,

Charles A. Whittaker

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Апрель 12, 2023

Prolonged cell cycle arrests occur naturally in differentiated cells and response to various stresses such as nutrient deprivation or treatment with chemotherapeutic agents. Whether how survive prolonged is not clear. Here, we used

Язык: Английский

Процитировано

10
Single Cell‐Inductively Coupled Plasma‐Time‐of‐Flight Mass Spectrometry for the Multiplexed Determination of Proteins DOI
Paula Menero‐Valdés, Beatriz Fernández, Rosario Pereiro

и другие.

Encyclopedia of Analytical Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 22

Опубликована: Март 27, 2025

Abstract The analysis of proteins in single cells has gained importance the past years because its application biomedical field for study disease pathogenesis, search biomarkers, identification drug targets, and action efficacy, among others. In particular, use sc‐ICP‐TOFMS technique combined with metal‐tagged antibodies allows multiplexed determination target proteins. Moreover, after appropriate labeling, this can provide also information regarding cell size, viability, cycle stage. Here, an overview working principle several considerations which must be taken into account, to obtain accurate reproducible data are presented. effects choice sample introduction system, metal tag obtention metal‐labeled immunoprobes, dwell preparation samples discussed chapter.

Язык: Английский

Процитировано

0
Causal role of immune cells in chronic periodontitis: a bidirectional Mendelian randomization study DOI Creative Commons
Yu Chen,

Xinyang Jin,

Qi Wang

и другие.

BMC Oral Health, Год журнала: 2024, Номер 24(1)

Опубликована: Июль 16, 2024

Abstract Background This study aims to explore the bidirectional causal relationship between immune cell phenotypes and chronic periodontitis using a Mendelian randomization framework. Materials methods Through two-sample analysis, this research examined genetic data related 731 traits periodontitis. Instrumental variables were chosen based on their links either or Various statistical techniques, including MR-Egger regression, weighted median, inverse-variance (IVW) employed determine connections. Results Predominantly IVW method, 26 distinct identified as potentially influencing ( P < 0.05). Conversely, affected 33 different The results for pleiotropy sensitivity tests stable. However, these associations lost significance after adjusting False Discovery Rate. Conclusion uncovers complex certain periodontitis, underscoring intricate interaction system pathogenesis of periodontal disease.

Язык: Английский

Процитировано

3
Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells DOI Open Access
Michael C. Lanz, Shuyuan Zhang, Matthew P. Swaffer

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 19, 2023

SUMMARY Cell size is tightly controlled in healthy tissues and single-celled organisms, but it remains unclear how influences cell physiology. Increasing was recently shown to remodel the proteomes of cultured human cells, demonstrating that large small cells same type can be biochemically different. Here, we corroborate these results mouse hepatocytes extend our analysis using yeast. We find size-dependent proteome changes are highly conserved mostly independent metabolic state. As eukaryotic grow larger, dilution genome elicits a starvation-like phenotype, suggesting growth limited by manner analogous limiting nutrient. also this phenomenon explains many proteomic ascribed yeast aging. Overall, data suggest concentration universal determinant content growing cells.

Язык: Английский

Процитировано

7