Cytoskeleton Response to Ionizing Radiation: A Brief Review on Adhesion and Migration Effects

Verde, Giuseppe La; Artiola, Valeria; Panzetta, Valeria; Pugliese, M.; Netti, Paolo Antonio; Fusco, Sabato

doi:10.3390/biomedicines9091102

Cited by 15 publications

(17 citation statements)

References 181 publications

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“…In particular, the reduced expression of YAP and its translocation into the nucleus could be a mechanism by which healthy cells protect themselves from apoptosis ( Zhang et al, 2012 ) and control their growth (increased

associates also with growth process). On the other side, the YAP nuclear exclusion/reduction can result in a temporary confined inhibition of cell proliferation and invasion, as supported by previous findings ( Panzetta et al, 2020 ; La Verde et al, 2021 ), but more importantly in a modulation of cell sensitivity to radiation ( Tsujiura et al, 2014 ) that can be used in the design of doses and timing of subsequent radiation therapy.…”

Section: Discussionsupporting

confidence: 75%

“…It is nowadays well established a direct connection between the development of cancer and the alteration in the components of the cytoskeleton (CSK) ( Hall, 2009 ; Panzetta et al, 2017 ), a structure that regulates several biological processes ( Krieg et al, 2019 ; Ladoux and Mège, 2017 ). Specifically, during cancer transformation, the CSK is subjected to modifications in its arrangement and composition, generally accompanied by a lowering of the cell mechanical properties ( Yilmaz and Christofori, 2009 ; La Verde et al, 2021 ). The reorganization of the CSK in tumour cells may results in epithelial-mesenchymal transition (EMT), which can promote cell migration and tumour invasiveness.…”

Section: Introductionmentioning

confidence: 99%

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Radiation therapy affects YAP expression and intracellular localization by modulating lamin A/C levels in breast cancer

Verde

Artiola

Pugliese

et al. 2022

Front. Bioeng. Biotechnol.

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The microenvironment of breast cancer actively participates in tumorigenesis and cancer progression. The changes observed in the architecture of the extracellular matrix initiate an oncogene-mediated cell reprogramming, that leads to a massive triggering of YAP nuclear entry, and, therefore, to cancer cell proliferation, invasion and probably to increased radiation-resistance. However, it is not yet fully understood how radiotherapy regulates the expression and subcellular localization of YAP in breast cancer cells experiencing different microenvironmental stiffnesses. To elucidate the role of extracellular matrix stiffness and ionizing radiations on YAP regulation, we explored the behaviour of two different mammary cell lines, a normal epithelial cell line (MCF10A) and a highly aggressive and invasive adenocarcinoma cell line (MDA-MB-231) interacting with polyacrylamide substrates mimicking the mechanics of both normal and tumour tissues (∼1 and ∼13 kPa). We report that X-ray radiation affected in a significant way the levels of YAP expression, density, and localization in both cell lines. After 24 h, MCF10A and MDA-MB-231 increased the expression level of YAP in both nucleus and cytoplasm in a dose dependent manner and particularly on the stiffer substrates. After 72 h, MCF10A reduced mostly the YAP expression in the cytoplasm, whereas it remained high in the nucleus of cells on stiffer substrates. Tumour cells continued to exhibit higher levels of YAP expression, especially in the cytoplasmic compartment, as indicated by the reduction of nuclear/cytoplasmic ratio of total YAP. Then, we investigated the existence of a correlation between YAP localization and the expression of the nuclear envelope protein lamin A/C, considering its key role in modulating nuclear deformability and changes in YAP shuttling phenomena. As supposed, we found that the effects of radiation on YAP nucleus/cytoplasmic expression ratio, increasing in healthy cells and decreasing in tumour ones, were accompanied by lower and higher lamin A/C levels in MCF10A and MDA-MB-231 cells, respectively. These findings point to obtain a deeper knowledge of the role of the extracellular matrix and the effects of X-rays on YAP and lamin A/C expression that can be used in the design of doses and timing of radiation therapy.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Radiation therapy affects YAP expression and intracellular localization by modulating lamin A/C levels in breast cancer

Verde

Artiola

Pugliese

et al. 2022

Front. Bioeng. Biotechnol.

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“…For a review of IR-effects on the cytoskeleton of animal tissues, primarily regarding the mechanisms of cellular adhesion and migration, see [16].…”

Section: Introductionmentioning

confidence: 99%

Effects of Environmental Stress Factors on the Actin Cytoskeleton of Fungi and Plants: Ionizing Radiation and ROS

Stephan

2023

Preprint

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Actin is an abundant and multifaceted protein in eukaryotic cells that has been detected in the cytoplasm as well as in the nucleus. In cooperation with numerous interacting accessory-proteins, monomeric actin (G-actin) polymerizes into microfilaments (F-actin) which constitute ubiquitous subcellular higher order structures. Considering the extensive spatial dimensions and multifunctionality of actin super-arrays, the present study analyses the issue if and to what extent environmental stress factors, specifically ionizing radiation (IR) and reactive oxygen species (ROS), affect the cellular actin-entity. In that context, this review particularly surveys IR-response of fungi and plants. It examines in detail which actin-related cellular constituents and molecular pathways are influenced by ionizing radiation and related ROS. This comprehensive survey concludes that the general integrity of the total cellular actin cytoskeleton is a requirement for IR-tolerance. Actin´s functions in genome organization and nuclear events like chromatin remodelling, DNA-repair, and transcription play a key role. Beyond that, it is highly significant that the macromolecular cytoplasmic and cortical actin-frameworks are affected by IR as well. In response to IR, actin-filament bundling proteins (fimbrins) are required to stabilize cables or patches. In addition, the actin-associated factors mediating cellular polarity are essential for IR-survivability. Moreover, it is concluded that a cellular homeostasis system comprising ROS, ROS-scavengers, NADPH-oxidases, and the actin cytoskeleton plays an essential role here. Consequently, besides the actin-fraction which controls crucial genome-integrity, also the portion which facilitates orderly cellular transport and polarized growth has to be maintained in order to survive IR.

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“…For a review of IR-effects on the cytoskeleton of animal tissues, primarily regarding the mechanisms of cellular adhesion and migration, see La Verde et al (2021).…”

mentioning

confidence: 99%

Effects of environmental stress factors on the actin cytoskeleton of fungi and plants: Ionizing radiation and ROS

Stephan

2023

Cytoskeleton

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Actin is an abundant and multifaceted protein in eukaryotic cells that has been detected in the cytoplasm as well as in the nucleus. In cooperation with numerous interacting accessory‐proteins, monomeric actin (G‐actin) polymerizes into microfilaments (F‐actin) which constitute ubiquitous subcellular higher order structures. Considering the extensive spatial dimensions and multifunctionality of actin superarrays, the present study analyses the issue if and to what extent environmental stress factors, specifically ionizing radiation (IR) and reactive oxygen species (ROS), affect the cellular actin‐entity. In that context, this review particularly surveys IR‐response of fungi and plants. It examines in detail which actin‐related cellular constituents and molecular pathways are influenced by IR and related ROS. This comprehensive survey concludes that the general integrity of the total cellular actin cytoskeleton is a requirement for IR‐tolerance. Actin's functions in genome organization and nuclear events like chromatin remodeling, DNA‐repair, and transcription play a key role. Beyond that, it is highly significant that the macromolecular cytoplasmic and cortical actin‐frameworks are affected by IR as well. In response to IR, actin‐filament bundling proteins (fimbrins) are required to stabilize cables or patches. In addition, the actin‐associated factors mediating cellular polarity are essential for IR‐survivability. Moreover, it is concluded that a cellular homeostasis system comprising ROS, ROS‐scavengers, NADPH‐oxidases, and the actin cytoskeleton plays an essential role here. Consequently, besides the actin‐fraction which controls crucial genome‐integrity, also the portion which facilitates orderly cellular transport and polarized growth has to be maintained in order to survive IR.

show abstract

Cytoskeleton Response to Ionizing Radiation: A Brief Review on Adhesion and Migration Effects

Cited by 15 publications

References 181 publications

Radiation therapy affects YAP expression and intracellular localization by modulating lamin A/C levels in breast cancer

Radiation therapy affects YAP expression and intracellular localization by modulating lamin A/C levels in breast cancer

Effects of Environmental Stress Factors on the Actin Cytoskeleton of Fungi and Plants: Ionizing Radiation and ROS

Effects of environmental stress factors on the actin cytoskeleton of fungi and plants: Ionizing radiation and ROS

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