2018
DOI: 10.1038/s41467-018-05367-2
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The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion

Abstract: Estrogen promotes growth of estrogen receptor-positive (ER+) breast tumors. However, epidemiological studies examining the prognostic characteristics of breast cancer in postmenopausal women receiving hormone replacement therapy reveal a significant decrease in tumor dissemination, suggesting that estrogen has potential protective effects against cancer cell invasion. Here, we show that estrogen suppresses invasion of ER+ breast cancer cells by increasing transcription of the Ena/VASP protein, EVL, which promo… Show more

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Cited by 63 publications
(51 citation statements)
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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%
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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%
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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%
“…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%