The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion

Padilla‐Rodriguez, Marco; Parker, Sara S.; Adams, Deanna G.; Westerling, Thomas; Puleo, Julieann; Watson, Adam W.; Hill, Samantha M.; Noon, Muhammad; Gaudin, Raphaël; Aaron, Jesse; Tong, Daoqin; Roe, Denise J.; Knudsen, Beatrice S.; Mouneimne, Ghassan

doi:10.1038/s41467-018-05367-2

Cited by 58 publications

(49 citation statements)

References 43 publications

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“…Our data suggest that EVL promotes durotactic invasion into 3D matrix; this is consistent with its essential role in mechanosensing and mechanically directed motility and highlights the significance of these processes for durotactic invasion. Importantly, we show that suppression of EVL expression enhances invasion into uniformly soft 3D matrix, which is consistent with our previous work demonstrating that EVL plays a suppressive role in breast cancer cell invasion (Mouneimne et al, 2012;Padilla-Rodriguez et al, 2018). These data emphasize a role for EVL in specifically mediating a response to mechanical stimulation, as opposed to promoting migration and invasion in general.…”

Section: Evl Specifically Promotes Durotactic Invasionsupporting

confidence: 92%

“…8, e and f). These results suggest that, without the challenge of a stiffness gradient, EVL KD cells are more invasive, which is consistent with previous work (Mouneimne et al, 2012;Padilla-Rodriguez et al, 2018) and highlights the specific involvement of EVL in durotactic invasion. Importantly, using gelatin zymography to measure the ability to degrade collagen, we found no significant difference in proteolytic activity between control and EVL KD cells; this suggests that the suppression of durotactic invasion in EVL KD cells is not caused by inhibition of matrix degradation (Fig.…”

Section: Evl Promotes Durotactic Invasion Within 3d Matrixsupporting

confidence: 92%

“…Invasion assays were modified from Padilla-Rodriguez et al (2018). Chambered 1.5 coverglass (Lab-Tek) was treated with silane and glutaraldehyde (see Preparation of deformable hydrogels) and sterilized under UV light for 15 min.…”

Section: D Invasion Assaysmentioning

confidence: 99%

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Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions

Puleo

Parker

Roman

et al. 2019

Journal of Cell Biology

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The mechanical properties of a cell’s microenvironment influence many aspects of cellular behavior, including cell migration. Durotaxis, the migration toward increasing matrix stiffness, has been implicated in processes ranging from development to cancer. During durotaxis, mechanical stimulation by matrix rigidity leads to directed migration. Studies suggest that cells sense mechanical stimuli, or mechanosense, through the acto-myosin cytoskeleton at focal adhesions (FAs); however, FA actin cytoskeletal remodeling and its role in mechanosensing are not fully understood. Here, we show that the Ena/VASP family member, Ena/VASP-like (EVL), polymerizes actin at FAs, which promotes cell-matrix adhesion and mechanosensing. Importantly, we show that EVL regulates mechanically directed motility, and that suppression of EVL expression impedes 3D durotactic invasion. We propose a model in which EVL-mediated actin polymerization at FAs promotes mechanosensing and durotaxis by maturing, and thus reinforcing, FAs. These findings establish dynamic FA actin polymerization as a central aspect of mechanosensing and identify EVL as a crucial regulator of this process.

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Section: Evl Specifically Promotes Durotactic Invasionsupporting

confidence: 92%

Section: Evl Promotes Durotactic Invasion Within 3d Matrixsupporting

confidence: 92%

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Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions

Puleo

Parker

Roman

et al. 2019

Journal of Cell Biology

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“…In this context, a recent study demonstrated that estrogen receptor-positive BCCs stimulated with estrogen showed impaired cell invasion and metastases through up-regulation of the actin-related protein EVL. This protein in turn promotes the formation of cortical actin bundles suppressing cell migration (Padilla-Rodriguez et al, 2018). Our findings refer to a different class of breast cancer and highlight a completely different mechanism of action.…”

Section: Discussionmentioning

confidence: 63%

Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling

et al. 2020

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Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.

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“…Indeed, numerous studies have demonstrated that the actin cytoskeleton of basal and luminal breast cancer cells shows structural and functional differences that result e.g. in an increased actin response in the interaction of breast cancer cells with natural killer cells 51 , in differential nuclear shape dynamics 52 , in the suppression of invasion 53 , and in cell fusion and the formation of cancer hybrid cells 54 . Other SETD proteins such as SETD5 have been associated with the invasion and migration of non-small cell lung cancer cells 55 .…”

Section: Discussionmentioning

confidence: 99%

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

Hassan

Rutsch

Győrffy

et al. 2020

Sci Rep

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In several carcinomas, the SET Domain Containing 3, Actin Histidine Methyltransferase (SETD3)is associated with oncogenesis. However, there is little knowledge about the role of SETD3 in the progression and prognosis of breast cancer. In this study, we first analyzed the prognostic value of SETD3 in breast cancer patients using the database of the public Kaplan-Meier plotter. Moreover, in vitro assays were performed to assess the role of SETD3 in the viability and capacity of invasion of human breast cancer cell lines. We observed that the high expression of SETD3 was associated with better relapse-free survival (RFS) of the whole collective of 3,951 patients, of Estrogen Receptorpositive, and of Luminal A-type breast cancer patients. However, in patients lacking expression of estrogen-, progesterone-and HER2-receptor, and those affected by a p53-mutation, SETD3 was associated with poor RFS. In vitro analysis showed that SETD3 siRNA depletion affects the viability of triple-negative cells as well as the cytoskeletal function and capacity of invasion of highly invasive MDA-MB-231 cells. Interestingly, SETD3 regulates the expression of other genes associated with cancer such as β-actin, FOXM1, FBXW7, Fascin, eNOS, and MMP-2. Our study suggests that SETD3 expression can act as a subtype-specific biomarker for breast cancer progression and prognosis.MTT proliferation assay. SETD3 depleted cells or controls (5 × 10 3 ) were plated in 96-well plates with DMEM medium (without phenol red) (Gibco ® , cat. No. 31053028, Germany) with FCS and incubated for 96 hours. After the incubation time, the medium was removed completely and cells were incubated with 20 µl/well of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) (cat. No. M2128-1G), at 5 mg/ml for 4 hours, at 37 °C. Subsequently, 100 µl of Stopping buffer, pH 4.7 composed of 10% (w/v) sodium dodecyl sulfate (SDS) (cat. No. 3599286) and 50% (v/v) N,) was added to stop the reaction and dissolve the formazan crystals. The absorbance was measured in a VersaMax ® Microplate Reader (Molecular Devices, Sunnyvale, CA, USA) at a wavelength of 595 nm. The proliferation of the control cells was defined as 100%. Results were derived from three independent sets of triplicate experiments. MTT, SDS, and N,N-Dimethyl formamide were from Sigma-

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The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion

Cited by 58 publications

References 43 publications

Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions

Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions

Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

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