MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation DOI

Weiwei Ren,

Rebeca Kawahara, Kenichi Suzuki

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(3)

Published: Jan. 3, 2025

Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic produced by lysosomal glycosidases secreted via exocytosis. Interestingly, exocytosis preferentially occurred vicinity focal adhesions, protein complexes connecting actin cytoskeleton to extracellular matrix. Through genome-wide knockout screening, identified MYO18B, an crosslinker, is required for adhesion maturation, facilitating release milieu. Moreover, mechanosensitive cation channel PIEZO1 locally activated at adhesions imports Ca2+ necessary lysosome-plasma membrane fusion. Collectively, our study unveiled intimate relationship between adhesion, shedding light unexpected interplay activities cellular mechanosensing.

Language: Английский

Modeling the extracellular matrix in cell migration and morphogenesis: a guide for the curious biologist DOI Creative Commons
Rebecca M. Crossley, Samuel Johnson, Erika Tsingos

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 1, 2024

The extracellular matrix (ECM) is a highly complex structure through which biochemical and mechanical signals are transmitted. In processes of cell migration, the ECM also acts as scaffold, providing structural support to cells well points potential attachment. Although well-studied structure, its role in many biological remains difficult investigate comprehensively due complexity variation within an organism. tandem with experiments, mathematical models helpful refining testing hypotheses, generating predictions, exploring conditions outside scope experiments. Such can be combined calibrated vivo vitro data identify critical cell-ECM interactions that drive developmental homeostatic processes, or progression diseases. this review, we focus on computational such migration including cancer metastasis, tissue morphogenesis. By highlighting predictive power these models, aim help bridge gap between experimental approaches studying provide guidance selecting appropriate model framework complement corresponding studies.

Language: Английский

Citations

25

Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy DOI Creative Commons
Jiaqiang Xiong, Rourou Xiao, Jiahui Zhao

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 21, 2024

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by stiffness solid tumors often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors corresponding mechanotransducers the cytoplasm, modulating phenotype of TAMs. Currently, tuning TAM polarization through stimulation has received increasing attention, whereas its effect on fate rarely been summarized. A better understanding relationship between will contribute to development new strategies for cancer therapy. In this review, we first introduced overall stiffness, analyzed changes mediated tumor progression, finally summarized effects targeting prognosis provide insight into field.

Language: Английский

Citations

20

Mime: A flexible machine-learning framework to construct and visualize models for clinical characteristics prediction and feature selection DOI Creative Commons
Hongwei Liu, Wei Zhang, Yihao Zhang

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 23, P. 2798 - 2810

Published: June 29, 2024

The widespread use of high-throughput sequencing technologies has revolutionized the understanding biology and cancer heterogeneity. Recently, several machine-learning models based on transcriptional data have been developed to accurately predict patients' outcome clinical response. However, an open-source R package covering state-of-the-art algorithms for user-friendly access yet be developed. Thus, we proposed a flexible computational framework construct machine learning-based integration model with elegant performance (Mime). Mime streamlines process developing predictive high accuracy, leveraging complex datasets identify critical genes associated prognosis. An in silico combined de novo PIEZO1-associated signatures constructed by demonstrated accuracy predicting outcomes patients compared other published models. Furthermore, could also precisely infer immunotherapy response applying different Mime. Finally, SDC1 selected from potential as glioma target. Taken together, our provides solution constructing will greatly expanded provide valuable insights into current fields. is available GitHub (https://github.com/l-magnificence/Mime).

Language: Английский

Citations

19

Infrared nanosensors of piconewton to micronewton forces DOI
Natalie Fardian‐Melamed, Artiom Skripka,

Benedikt Ursprung

et al.

Nature, Journal Year: 2025, Volume and Issue: 637(8044), P. 70 - 75

Published: Jan. 1, 2025

Language: Английский

Citations

8

MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation DOI

Weiwei Ren,

Rebeca Kawahara, Kenichi Suzuki

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(3)

Published: Jan. 3, 2025

Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic produced by lysosomal glycosidases secreted via exocytosis. Interestingly, exocytosis preferentially occurred vicinity focal adhesions, protein complexes connecting actin cytoskeleton to extracellular matrix. Through genome-wide knockout screening, identified MYO18B, an crosslinker, is required for adhesion maturation, facilitating release milieu. Moreover, mechanosensitive cation channel PIEZO1 locally activated at adhesions imports Ca2+ necessary lysosome-plasma membrane fusion. Collectively, our study unveiled intimate relationship between adhesion, shedding light unexpected interplay activities cellular mechanosensing.

Language: Английский

Citations

4