Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis

Torrino, Stéphanie; Grasset, Eloïse M.; Audebert, Stéphane; Belhadj, Ilyes; Lacoux, Caroline; Haynes, Meagan Campol; Pisano, Sabrina; Abélanet, Sophie; Brau, Frédéric; Chan, Stephen Y.; Mari, Bernard; Oldham, William M.; Ewald, Andrew J.; Bertero, Thomas

doi:10.1016/j.cmet.2021.05.009

Cited by 85 publications

(53 citation statements)

References 82 publications

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“…However, the data obtained indicate that the main protein content and gene expression of microtubules, alpha-and beta-tubulin, in these cases are reduced. Microtubules are directly involved in the division process, forming the division spindle and thus, are involved in tumor pathogenesis [41,42]. Reducing the formation of microtubules significantly improves the prognosis in cancer [43,44].…”

Section: Discussionmentioning

confidence: 99%

Organization of the Cytoskeleton in Ectopic Foci of the Endometrium with Rare Localization

Toniyan

Povorova²,

Gorbacheva³

et al. 2021

Biomedicines

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(1) Background: Endometriosis is a common pathology of the female reproductive system, often accompanied by pain and decreased fertility. However, its pathogenesis has not been sufficiently studied regarding the role of the cytoskeleton. In this study, we describe two clinical cases involving rare localization of extragenital endometriosis (umbilicus) and compare them with genital endometriosis of different localization (ovaries and uterus), as well as eutopic endometrium obtained with separate diagnostic curettage without confirmed pathology. (2) Methods: The relative content of actin and tubulin cytoskeleton proteins was determined by Western blotting, and the expression of genes encoding these proteins was determined by RT-PCR in the obtained intraoperative biopsies. The content of 5hmC was estimated by dot blot experiments, and the methylase/demethylase and acetylase/deacetylase contents were determined. (3) Results: The obtained results indicate that the content of the actin-binding protein alpha-actinin1 significantly increased (p < 0.05) in the groups with endometriosis, and this increase was most pronounced in patients with umbilical endometriosis. In addition, both the mRNA content of the ACTN1 gene and 5hmC content increased. It can be assumed that the increase in 5hmC is associated with a decrease in the TET3 demethylase content. Moreover, in the groups with extragenital endometriosis, alpha- and beta-tubulin content was decreased (p < 0.05) compared to the control levels. (4) Conclusions: In analyzing the results, further distance of ectopic endometrial foci from the eutopic localization may be associated with an increase in the content of alpha-actinin1, probably due to an increase in the expression of its gene and an increase in migration potential. In this case, a favorable prognosis can be explained by a decrease in tubulin content and, consequently, a decrease in the rate of cell division.

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Section: Discussionmentioning

confidence: 99%

Organization of the Cytoskeleton in Ectopic Foci of the Endometrium with Rare Localization

Toniyan

Povorova²,

Gorbacheva³

et al. 2021

Biomedicines

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“…Rafiq et al showed that microtubules modify both focal adhesions and podosomes via KANK proteins to regulate the actomyosin cytoskeleton [ 16 ]. In a breast cancer model, matrix stiffening promoted glutamylation of microtubules to affect their mechanical stability [ 17 ]. Joca et al showed that increased stretching of cardiomyocytes induced microtubule-dependent changes in NADPH oxidase and reactive oxygen species [ 18 ].…”

Section: Role Of the Cytoskeleton In Mechanotransductionmentioning

confidence: 99%

Mechanotransduction at the Plasma Membrane-Cytoskeleton Interface

Uray

2021

IJMS

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Mechanical cues are crucial for survival, adaptation, and normal homeostasis in virtually every cell type. The transduction of mechanical messages into intracellular biochemical messages is termed mechanotransduction. While significant advances in biochemical signaling have been made in the last few decades, the role of mechanotransduction in physiological and pathological processes has been largely overlooked until recently. In this review, the role of interactions between the cytoskeleton and cell-cell/cell-matrix adhesions in transducing mechanical signals is discussed. In addition, mechanosensors that reside in the cell membrane and the transduction of mechanical signals to the nucleus are discussed. Finally, we describe two examples in which mechanotransduction plays a significant role in normal physiology and disease development. The first example is the role of mechanotransduction in the proliferation and metastasis of cancerous cells. In this system, the role of mechanotransduction in cellular processes, including proliferation, differentiation, and motility, is described. In the second example, the role of mechanotransduction in a mechanically active organ, the gastrointestinal tract, is described. In the gut, mechanotransduction contributes to normal physiology and the development of motility disorders.

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“…Since external mechanical forces are responsible for rapid cytoskeleton rearrangement, we first stained F-actin in control and CM-stressed MDA-MB-231 cells 34 . This revealed a high degree of anisotropy in CM cells, with an increased number of stress fibres following CM, in addition to more abundant filopodia ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Confined migration promotes cancer metastasis through resistance to anoikis and increased invasiveness

Fanfone

Mammi

et al. 2021

Preprint

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Mechanical stress is known to fuel several hallmarks of cancer, ranging from genome instability to uncontrolled proliferation or invasion. Cancer cells are constantly challenged by mechanical stresses not only in the primary tumour but also during metastasis. However, this latter has seldom been studied with regards to mechanobiology, in particular resistance to anoikis, a cell death programme triggered by loss of cell adhesion. Here, we show in vitro that migrating breast cancer cells develop resistance to anoikis following their passage through microporous membranes mimicking confined migration (CM), a mechanical constriction that cancer cells encounter during metastasis. This CM-induced resistance was mediated by Inhibitory of Apoptosis Proteins (IAPs), and sensitivity to anoikis could be restored after their inhibition using SMAC mimetics. Anoikis-resistant mechanically-stressed cancer cells displayed enhanced cell motility and evasion from natural killer cell-mediated immune surveillance, as well as a marked advantage to form lung metastatic lesions in mice. Our findings reveal that CM increases the metastatic potential of breast cancer cells.

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Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis

Cited by 85 publications

References 82 publications

Organization of the Cytoskeleton in Ectopic Foci of the Endometrium with Rare Localization

Organization of the Cytoskeleton in Ectopic Foci of the Endometrium with Rare Localization

Mechanotransduction at the Plasma Membrane-Cytoskeleton Interface

Confined migration promotes cancer metastasis through resistance to anoikis and increased invasiveness

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