The multiple roles of actin-binding proteins at invadopodia

Mgrditchian, Takouhie; Sakalauskaite, Gabriele; Müller, Tanja; Hoffmann, Céline; Thomas, Clément

doi:10.1016/bs.ircmb.2021.03.004

Cited by 9 publications

(4 citation statements)

References 232 publications

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“…Here, we report that HTRA1 depletion significantly inhibited the migration and invasion abilities of GBM cells, and mesenchymal markers, including ZEB1, N‐cadherin, vimentin, fibronectin and CD44, decreased, while the epithelial marker E‐cadherin increased. Changes in the F‐actin cytoskeleton was consistent with the suppression of the formation of invadopodia, which are protrusions of the cell membrane that are rich in F‐actin and facilitate the dissemination of tumor cells 45 . Previous reports indicate that HDAC6 is involved in cytoskeletal organization as well as invadopodia formation through deacetylation of α‐tubulin 40 .…”

Section: Discussionsupporting

confidence: 68%

“…Changes in the F-actin cytoskeleton was consistent with the suppression of the formation of invadopodia, which are protrusions of the cell membrane that are rich in F-actin and facilitate the dissemination of tumor cells. 45 Previous reports indicate that HDAC6 is involved in cytoskeletal organization as well as invadopodia formation through deacetylation of α-tubulin. 40 HDAC6 is a member of the HDAC family that is mainly located in the cytoplasm and promotes tumor cell migration and invasion through deacetylation of α-tubulin and cortactin, which destabilizes the cytoskeleton.…”

Section: Discussionmentioning

confidence: 99%

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HTRA1 promotes EMT through the HDAC6/Ac‐α‐tubulin pathway in human GBM cells

Zhao,

Wu,

Wang

et al. 2024

CNS Neurosci Ther

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BackgroundThe infiltrative nature of human gliomas renders complete surgical removal of tumors futile. Thus, illuminating mechanisms of their infiltrative properties may improve therapies and outcomes of glioma patients.MethodsComprehensive bioinformatic analyses of PRSS family were undertaken. Transfection of HTRA1 siRNAs was used to suppress HTRA1 expression. CCK‐8, EdU, and colony formation assay were employed to assess cell viability, and cell migration/invasion was detected by transwell, wound healing, and 3D tumor spheroid invasion assays. Immunoprecipitation was applied to study the mechanism that HTRA1 affected cell migration. In addition, in situ xenograft tumor model was employed to explore the role of HTRA1 in glioma growth in vivo.ResultsHTRA1 knockdown could lead to suppression of cell viability, migration and invasion, as well as increased apoptosis. Immunoprecipitation results indicates HTRA1 might facilitate combination between HDAC6 and α‐tubulin to enhance cell migration by decreasing α‐tubulin acetylation. Besides, HTRA1 knockdown inhibited the growth of xenografts derived from orthotopic implantation of GBM cells and prolonged the survival time of tumor‐bearing mice.ConclusionOur results indicate that HTRA1 promotes the proliferation and migration of GBM cells in vitro and in vivo, and thus may be a potential target for treatment in gliomas.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

HTRA1 promotes EMT through the HDAC6/Ac‐α‐tubulin pathway in human GBM cells

Zhao,

Wu,

Wang

et al. 2024

CNS Neurosci Ther

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“…In general, cell-substrate adhesion is formed by the binding of specific transmembrane signaling molecules such as integrin to extracellular matrix (ECM), which initiates intracellular network signaling leading to actin-polymerization driven lamellipodia formation and cell migration on the ECM substrate ( Mgrditchian et al, 2021 ; Thompson et al, 2021 ). Under cell-substrate adhesion condition, the lamellipodia formation at the cell’s front edge is stimulated by Rac-1 activation ( Mehidi et al, 2019 ; Schaks et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

A Portable Controllable Compressive Stress Device to Monitor Human Breast Cancer Cell Protrusions at Single-Cell Resolution

Yeh

Juang

Chen

et al. 2022

Front. Bioeng. Biotechnol.

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In vitro devices offer more numerous methods than in vivo models to investigate how cells respond to pressure stress and quantify those responses. Several in vitro devices have been developed to study the cell response to compression force. However, they are unable to observe morphological changes of cells in real-time. There is also a concern about cell damage during the process of harvesting cells from 3D gels. Here we report a device employing transparent, thin gel layers to clamp cells between the interfaces and applied a controllable compression force by stacking multiple layers on the top. In this approach, cells can be monitored for alteration of cellular protrusions, whose diversity has been proven to promote cancer cell dissemination, with single-cell resolution under compression force. Furthermore, p-Rac-1 and rhodamine staining on the device directly to confirm the actin filaments of lamellipodia. The method was able to fulfill real-time live-cell observation at single-cell resolution and can be readily used for versatile cell analysis. MDA-MB-231 and MCF7 breast cancer cells were utilized to demonstrate the utility of the device, and the results showed that the stimuli of compression force induce MDA-MB-231 and MCF7 to form lamellipodia and bleb protrusions, respectively. We envision the device may be used as a tool to explore mechanisms of membrane protrusion transitions and to screen drug candidates for inhibiting cancer cell protrusion plasticity for cancer therapy.

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“…Invasive cancer cells possess specialized, actin-rich, membrane protrusions called invadopodia, which serve as a focal point for accumulating pro-invasive MMPs and other ECM-degrading enzymes ( Weaver, 2006 ; Jacob and Prekeris, 2015 ; Eddy et al, 2017 ; Mgrditchian et al, 2021 ). The concentration of membrane-bound MMPs and targeted release of soluble MMPs at invadopodia result in localized and potent degradation of the ECM, which facilitates tumor cell escape from the primary tumor, and invasion into and out of the vasculature.…”

Section: Introductionmentioning

confidence: 99%

Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus

Mgrditchian,

Brown-Clay,

Hoffmann

et al. 2023

Front. Cell Dev. Biol.

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The actin cytoskeleton plays a critical role in cancer cell invasion and metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate cancer cell invasion by focusing the secretion of extracellular matrix-degrading enzymes, including matrix metalloproteinases (MMPs). In this study, we investigated the nuclear role of cysteine-rich protein 2 (CRP2), a two LIM domain-containing F-actin-binding protein that we previously identified as a cytoskeletal component of invadopodia, in breast cancer cells. We found that F-actin depolymerization stimulates the translocation of CRP2 into the nucleus, resulting in an increase in the transcript levels of pro-invasive and pro-metastatic genes, including several members of the MMP gene family. We demonstrate that in the nucleus, CRP2 interacts with the transcription factor serum response factor (SRF), which is crucial for the expression of MMP-9 and MMP-13. Our data suggest that CRP2 and SRF cooperate to modulate of MMP expression levels. Furthermore, Kaplan-Meier analysis revealed a significant association between high-level expression of SRF and shorter overall survival and distant metastasis-free survival in breast cancer patients with a high CRP2 expression profile. Our findings suggest a model in which CRP2 mediates the coordination of cytoplasmic and nuclear processes driven by actin dynamics, ultimately resulting in the induction of invasive and metastatic behavior in breast cancer cells.

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The multiple roles of actin-binding proteins at invadopodia

Cited by 9 publications

References 232 publications

HTRA1 promotes EMT through the HDAC6/Ac‐α‐tubulin pathway in human GBM cells

HTRA1 promotes EMT through the HDAC6/Ac‐α‐tubulin pathway in human GBM cells

A Portable Controllable Compressive Stress Device to Monitor Human Breast Cancer Cell Protrusions at Single-Cell Resolution

Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus

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