The Role of the Actin Cytoskeleton in Cancer and Its Potential Use as a Therapeutic Target

Brayford, Simon; Schevzov, Galina; Vos, Julien A M; Gunning, Peter W.

doi:10.1007/978-1-4939-2904-7_16

Cited by 16 publications

(14 citation statements)

References 108 publications

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“…Our study concerned interactions between actin and isoflavones as potential ligands changing the ability of the protein to polymerize from the G to F form. Limiting the polymerization by binding active sites or by changing the conformation may reduce cancer cell migration and metastasis [ 8 ]. Polyphenols, including isoflavones, are potential actin ligands, although only genistein has been studied to date [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

“…Binding of nutraceuticals to actin at other sites is one potential mechanism that can limit actin polymerization, thus preventing cancer cell movement and cancer invasion. So far, little progress has been made in the search for compounds that disrupt the organization of actin filaments, although it is already known that cytoskeletal reorganization caused by the binding of ligands to actin allows not only the inhibition of migration but also apoptosis of cancer cells [ 8 , 9 , 10 ]. By binding to actin, nutraceuticals can modify and determine the intracellular location of transcription factors that play important roles in gene transcription [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Binding of Red Clover Isoflavones to Actin as A Potential Mechanism of Anti-Metastatic Activity Restricting the Migration of Cancer Cells

2018

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Actin functions are crucial for the ability of the cell to execute dynamic cytoskeleton reorganization and movement. Nutraceuticals that form complexes with actin and reduce its polymerization can be used in cancer therapy to prevent cell migration and metastasis of tumors. The aim of this study was to evaluate the ability of isoflavones to form complexes with actin. Docking simulation and isothermal titration calorimetry were used for this purpose. The formation of complexes by hydrogen bonds, hydrophobic and π-π interactions was demonstrated. Interactions occurred at the ATP binding site, which may limit the rotation of the actin molecule observed during polymerization and also at the site responsible for contacts during polymerization, reducing the ability of the molecule to form filaments. The greatest therapeutic potential was demonstrated by isoflavones occurring in red clover sprouts, i.e., biochanin A and formononetin, being methoxy derivatives of genistein and daidzein.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Binding of Red Clover Isoflavones to Actin as A Potential Mechanism of Anti-Metastatic Activity Restricting the Migration of Cancer Cells

2018

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“…3,4 The smaller Young's modulus and increased cell deformability are major characteristics of cancer cells. 11 Cross et al investigated the anticancer effect of green tea on regulating mechanical properties of live metastatic cancer cells through atomic force microscopy (AFM) analysis. 3,7 Young's modulus of highly invasive breast cancer cells was reported significantly lower than noninvasive breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, actin targeting has therapeutic potential and affects cell mechanics and consequently cell metastasis potential. 11 Cross et al investigated the anticancer effect of green tea on regulating mechanical properties of live metastatic cancer cells through atomic force microscopy (AFM) analysis. 12 They found that the stiffness of treated tumor cells increased significantly and concluded that restoration of mechanical properties might contribute to the inhibition of metastasis.…”

Section: Introductionmentioning

confidence: 99%

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Azadi

Tafazzoli-Shadpour

Soleimani

et al. 2019

J Biomedical Materials Res

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To date, a myriad of strategies has been suggested for targeting the chemical signaling of cancer cells. Also, biomechanical features are gaining much more attention. These features can be used as biomarkers which influence cancer progression. Current approaches on cancer treatment are mainly focused on changing the biochemical signaling of cancer cells, whereas less attention was devoted to their biomechanical properties. Herein, we propose targeting of cancer cell mechanics through the microenvironmental mechanical and chemical cues. As such, we examined the role of substrate stiffness as well as the effect of epidermal growth factor receptor (EGFR) blockade in the cell mechanics. As a mechanical stimulus, stiff and soft polydimethylsiloxane substrates were utilized, while as a chemical stimulus, EGFR blockade was considered. Thus, breast cancer cell lines, MCF7 and MDA‐MB‐231, were cultured among chemical and mechanical groups. The local elasticity of cancer cells was assessed by atomic force microscopy nanoindentation method. Furthermore, we evaluated the effect of mentioned mechanical and chemical treatments on the morphology, actin cytoskeleton structures, and cancer cell migration abilities. The stiffness and migration ability of cancer cells increased by substrate stiffening while Cetuximab treatment demonstrated an elevation in the elastic modulus of cells followed by a reduction in the migration ability. These findings indicate that cancer cell mechanics is modulated not only by the mechanical cues but also by the chemical ones through EGFR signaling pathway. Overall, our results illustrate that manipulation of cell mechanics allows for the possible modulation of tumor cell migration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1569–1581, 2019.

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“…Variation in the cytoskeleton organization, changes in the morphology of cells, motility and adhesiveness are characteristic features of transformed cancer cells. It has been shown in the literature that the cytoskeleton of cells can become promising targets in chemotherapy [54], but detailed analysis of this issue is beyond the scope of this manuscript.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Human Colon by Raman Spectroscopy and Imaging-Elucidation of Biochemical Changes in Carcinogenesis

Brożek-Płuska

Musiał

Kordek

et al. 2019

IJMS

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Noninvasive Raman imaging of non-fixed and unstained human colon tissues based on vibrational properties of noncancerous and cancerous samples can effectively enable the differentiation between noncancerous and tumor tissues. This work aimed to evaluate the biochemical characteristics of colon cancer and the clinical merits of multivariate Raman image and spectroscopy analysis. Tissue samples were collected during routine surgery. The non-fixed, fresh samples were used to prepare micrometer sections from the tumor mass and the tissue from the safety margins outside of the tumor mass. Adjacent sections were used for typical histological analysis. We have found that the chemical composition identified by Raman spectroscopy of the cancerous and the noncancerous colon samples is sufficiently different to distinguish pathologically changed tissue from noncancerous tissue. We present a detailed analysis of Raman spectra for the human noncancerous and cancerous colon tissue. The multivariate analysis of the intensities of lipids/proteins/carotenoids Raman peaks shows that these classes of compounds can statistically divide analyzed samples into noncancerous and pathological groups, reaffirming that Raman imaging is a powerful technique for the histochemical analysis of human tissues. Raman biomarkers based on ratios for lipids/proteins/carotenoids content were found to be the most useful biomarkers in spectroscopic diagnostics.

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The Role of the Actin Cytoskeleton in Cancer and Its Potential Use as a Therapeutic Target

Cited by 16 publications

References 108 publications

Binding of Red Clover Isoflavones to Actin as A Potential Mechanism of Anti-Metastatic Activity Restricting the Migration of Cancer Cells

Binding of Red Clover Isoflavones to Actin as A Potential Mechanism of Anti-Metastatic Activity Restricting the Migration of Cancer Cells

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Analysis of Human Colon by Raman Spectroscopy and Imaging-Elucidation of Biochemical Changes in Carcinogenesis

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