Human cancer cells generate spontaneous calcium transients and intercellular waves that modulate tumor growth

Liang, Cheng; Zhang, Qian; Chen, Xin; Liu, Jiawei; Tanaka, Mai; Wang, Shu; Lepler, Sharon; Jin, Zeyuan; Siemann, Dietmar W.; Zeng, Bo; Tang, Xin

doi:10.1016/j.biomaterials.2022.121823

Cited by 9 publications

(7 citation statements)

References 127 publications

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“…PLX4032-induced increasing of actin stress fibers is necessary for the YAP activation [37]. Increasing of actin stress fibers can facilitate the mechano-sensing of the cells to altered ECM stiffness [58][59][60][61] and may further activate YAP [54][55][56][57]. These results demonstrate a closed feedback loop for ECMchemotherapy to influence each other in BRAF-mutant melanoma cancer cells mutually.…”

Section: Ecm Induces Yap Nuclear Translocation and Influences The Res...mentioning

confidence: 69%

“…In general, ECM stiffness (Young's modulus) is sensed by transmembrane integrins on the cell surface, which sequentially induce activation of Src, FAK at focal adhesion sites and intracellular Rho-ROCK machinery to increase cytoskeleton contractility, which is mechanical tension in cells generated by the sliding of actin and myosin filaments along each other [58][59][60][61]. As demonstrated by our own CRISPR/Cas9 imaging of real-time YAP dynamics and by other independent research groups, increased cytoskeleton contractility triggers nuclear translocation of YAP, while reduced contractility induces cytoplasmic retention of YAP [19,22,34,57,[62][63][64].…”

Section: Viscoelastic Mechanics Of Ecm Regulates Yapmentioning

confidence: 99%

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YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer

Huang,

Wang,

Mackey

et al. 2023

IJMS

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Biomechanical forces are of fundamental importance in biology, diseases, and medicine. Mechanobiology is an emerging interdisciplinary field that studies how biological mechanisms are regulated by biomechanical forces and how physical principles can be leveraged to innovate new therapeutic strategies. This article reviews state-of-the-art mechanobiology knowledge about the yes-associated protein (YAP), a key mechanosensitive protein, and its roles in the development of drug resistance in human cancer. Specifically, the article discusses three topics: how YAP is mechanically regulated in living cells; the molecular mechanobiology mechanisms by which YAP, along with other functional pathways, influences drug resistance of cancer cells (particularly lung cancer cells); and finally, how the mechanical regulation of YAP can influence drug resistance and vice versa. By integrating these topics, we present a unified framework that has the potential to bring theoretical insights into the design of novel mechanomedicines and advance next-generation cancer therapies to suppress tumor progression and metastasis.

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Section: Ecm Induces Yap Nuclear Translocation and Influences The Res...mentioning

confidence: 69%

Section: Viscoelastic Mechanics Of Ecm Regulates Yapmentioning

confidence: 99%

YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer

Huang,

Wang,

Mackey

et al. 2023

IJMS

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“…The mechanisms by which cells sense and transduce mechanical cues into biochemical signals and events are referred to as mechanotransduction. For example, recent data suggests that substrate stiffness can regulate the dynamics of intra/intracellular calcium signals [213]. On one hand, these two types of signaling share many common intracellular pathways and can work in parallel for the same function, such as force-induced Rac activation that is independent of canonical Src activity [214].…”

Section: The Crosstalk Between Mechanotransduction and Oncogenic Sign...mentioning

confidence: 99%

Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine

Xin,

Li,

Huang

et al. 2023

Oncogene

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Evidence from physical sciences in oncology increasingly suggests that the interplay between the biophysical tumor microenvironment and genetic regulation has significant impact on tumor progression. Especially, tumor cells and the associated stromal cells not only alter their own cytoskeleton and physical properties but also remodel the microenvironment with anomalous physical properties. Together, these altered mechano-omics of tumor tissues and their constituents fundamentally shift the mechanotransduction paradigms in tumorous and stromal cells and activate oncogenic signaling within the neoplastic niche to facilitate tumor progression. However, current findings on tumor biophysics are limited, scattered, and often contradictory in multiple contexts. Systematic understanding of how biophysical cues influence tumor pathophysiology is still lacking. This review discusses recent different schools of findings in tumor biophysics that have arisen from multi-scale mechanobiology and the cutting-edge technologies. These findings range from the molecular and cellular to the whole tissue level and feature functional crosstalk between mechanotransduction and oncogenic signaling. We highlight the potential of these anomalous physical alterations as new therapeutic targets for cancer mechanomedicine. This framework reconciles opposing opinions in the field, proposes new directions for future cancer research, and conceptualizes novel mechanomedicine landscape to overcome the inherent shortcomings of conventional cancer diagnosis and therapies.

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“…At the same time, it is necessary to release the links made between the cadherins between the cell fragments and viable cells [51], but it is critical that the connections between viable cells remain untouched [52,53]. If this intercellular detachment is achieved after the fragmentation of the debris under the extracellular matrix layer, agitation and mechanics of the culture medium (such as orbital stirrer or crop medium jets) place a higher degree of mechanical tension on the links between the cadherins that connect cellular debris to intact cells compared to the cadherins that bind living cells.…”

Section: Cellular Spotmentioning

confidence: 99%

“…The removal of cellular debris after catapulting involves vortex-type agitation [52,54]. This stage requires a thick support membrane in order to not put mechanical tension on the bonds between living cells.…”

Section: Cellular Spotmentioning

confidence: 99%

Perspectives on Scaffold Designs with Roles in Liver Cell Asymmetry and Medical and Industrial Applications by Using a New Type of Specialized 3D Bioprinter

Harbuz,

Banciu,

David

et al. 2023

IJMS

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Cellular asymmetry is an important element of efficiency in the compartmentalization of intracellular chemical reactions that ensure efficient tissue function. Improving the current 3D printing methods by using cellular asymmetry is essential in producing complex tissues and organs such as the liver. The use of cell spots containing at least two cells and basement membrane-like bio support materials allows cells to be tethered at two points on the basement membrane and with another cell in order to maintain cell asymmetry. Our model is a new type of 3D bioprinter that uses oriented multicellular complexes with cellular asymmetry. This novel approach is necessary to replace the sequential and slow processes of organogenesis with rapid methods of growth and 3D organ printing. The use of the extracellular matrix in the process of bioprinting with cells allows one to preserve the cellular asymmetry in the 3D printing process and thus preserve the compartmentalization of biological processes and metabolic efficiency.

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Human cancer cells generate spontaneous calcium transients and intercellular waves that modulate tumor growth

Cited by 9 publications

References 127 publications

YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer

YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer

Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine

Perspectives on Scaffold Designs with Roles in Liver Cell Asymmetry and Medical and Industrial Applications by Using a New Type of Specialized 3D Bioprinter

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