Silencing of LASP-1 influences zyxin localization, inhibits proliferation and reduces migration in breast cancer cells

Grünewald, Thomas G.P.; Kämmerer, Ulrike; Schulze, Elfriede; Schindler, Dorothee; Hönig, Arnd; Zimmer, Michael; Butt, Elke

doi:10.1016/j.yexcr.2005.12.016

Cited by 106 publications

(150 citation statements)

References 29 publications

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“…Consistent with these data, we just recently described the overexpression of LASP-1 to very high levels in breast carcinomas and lymph node metastases (Grunewald et al, 2006). The functional significance of LASP-1 in cancer metastasis is further supported by the presented data showing high LASP-1 expression in ovarian cancer tissue and reduced cell migration in ovarian cancer cells depleted of LASP-1.…”

Section: Discussionsupporting

confidence: 86%

“…In analogy to previous findings in myoepithelial cells of human breast tissue (Grunewald et al, 2006), a massive overexpression in vascular smooth muscle cells could be observed ( Figure 1C). …”

Section: Lasp-1 Is Overexpressed In Ovarian Cancer Tissuesupporting

confidence: 89%

“…The loss of zyxin at the sites of focal contacts without changing cellular zyxin protein levels is not restricted to cancer cells, but was also observed in human umbilical vein endothelial cells (Grunewald et al, 2006). Interestingly, in these cells, zyxin could still be detected along the actin stress fibres, indicating the potential existence of another zyxin-recruiting protein along actin stress fibres since earlier results detected LASP-1 only in the focal adhesion plaques (Chew et al, 2002;Butt et al, 2003).…”

Section: Discussionmentioning

confidence: 64%

“…Although the exact function of LASP-1 is not known, recent results suggest an important role for this protein in cell adhesion and migration (Butt et al, 2003;Lin et al, 2004;Grunewald et al, 2006;Nakagawa et al, 2006). To directly examine the relevance of LASP-1 for cell motility we performed migration experiments in a modified Boyden chamber with SKOV-3 cells either transfected with LASP-1 siRNA or zyxin siRNA to downregulate the respective protein.…”

Section: Silencing Of Lasp-1 But Not Of Zyxin Decreases Cell Migrationmentioning

confidence: 99%

“…Interestingly, recent work has shown, that knock-down of LASP-1 in metastatic breast cancer cell lines BT-20 and MCF-7 results in a strong inhibition of proliferation and migration and leads to a reduction of zyxin at focal contacts through absence of LASP-1 (Grunewald et al, 2006).…”

mentioning

confidence: 99%

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Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation

Grünewald

Kämmerer

Winkler³

et al. 2007

Br J Cancer

108

135

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LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration. In the present work, we analysed the effect of LASP-1 on biology and function of human ovarian cancer cell line SKOV-3 using small interfering RNA technique (siRNA).Transfection with LASP-1-specific siRNA resulted in a reduced protein level of LASP-1 in SKOV-3 cells. The siRNA-treated cells were arrested in G 2 /M phase of the cell cycle and proliferation of the tumour cells was suppressed by 60 -90% corresponding to around 70% of the cells being transfected successfully as seen by immunofluorescence. Moreover, transfected tumour cells showed a 40% reduced migration. LASP-1 silencing is accompanied by a reduced binding of the LASP-1-binding partner zyxin to focal contacts without changes in actin stress fibre and microtubule organisation or focal adhesion morphology as observed by immunofluorescence. In contrast, silencing of zyxin is not influencing cell migration and had neither influence on LASP-1 expression nor actin cytoskeleton and focal contact morphology suggesting that LASP-1 is necessary and sufficient for recruiting zyxin to focal contacts.The data provide evidence for an essential role of LASP-1 in tumour cell growth and migration, possibly through influencing zyxin localization.

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Section: Discussionsupporting

confidence: 86%

Section: Lasp-1 Is Overexpressed In Ovarian Cancer Tissuesupporting

confidence: 89%

Section: Discussionmentioning

confidence: 64%

Section: Silencing Of Lasp-1 But Not Of Zyxin Decreases Cell Migrationmentioning

confidence: 99%

mentioning

confidence: 99%

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Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation

Grünewald

Kämmerer

Winkler³

et al. 2007

Br J Cancer

108

135

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Ectopic expression of LIM‐nebulette (LASP2) reveals roles in cell migration and spreading

Deng

Norris

Panaviene

et al. 2008

Cell Motil. Cytoskeleton

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LIM-nebulette (LASP2) is a small focal adhesion protein and a member of the nebulin family of actin binding proteins. This recently identified splice variant of the nebulette locus is widely expressed and highly enriched in neuronal tissue. Other than the facts that LIM-nebulette is a focal adhesion protein and interacts with zyxin, nothing is known about its function. Given that LIM-nebulette has an identical modular organization and overlapping tissue distributions to that of LASP1, we have analyzed the role of LIM-nebulette in comparison with that of LASP1. We find that LIM-nebulette is a dynamic focal adhesion protein that increases the rate of attachment and spreading of fibroblasts on fibronectin coated surfaces. Additionally, LIM-nebulette is recruited from the cortical cytoskeleton in non-motile cells to focal adhesions at the leading edge of stimulated cells. In confluent cultures of HeLa and NIH3T3 cells, LIM-nebulette co-localizes with α-catenin in putative adherens junctions, whereas LASP1 is devoid of these areas. Interestingly, overexpression of LIM-nebulette in PC6 cells inhibits neurite outgrowth in response to growth factors. Collectively, our data indicate that LIM-nebulette and LASP1 have distinct roles in the actin cytoskeleton.

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Cytoplasmic Ig‐domain proteins: Cytoskeletal regulators with a role in human disease

Otey

Dixon²,

Stack

et al. 2009

Cell Motil. Cytoskeleton

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Immunoglobulin domains are found in a wide variety of functionally diverse transmembrane proteins, and also in a smaller number of cytoplasmic proteins. Members of this latter group are usually associated with the actin cytoskeleton, and most of them bind directly to either actin or myosin, or both. Recently, studies of inherited human disorders have identified disease-causing mutations in five cytoplasmic Ig-domain proteins: myosin-binding protein C, titin, myotilin, palladin, and myopalladin. Together with results obtained from cultured cells and mouse models, these clinical studies have yielded novel insights into the unexpected roles of Ig domain proteins in mechanotransduction and signaling to the nucleus. An emerging theme in this field is that cytoskeleton-associated Ig domain proteins are more than structural elements of the cell, and may have evolved to fill different needs in different cellular compartments. Cell Motil. Cytoskeleton 66: 618-634, 2009. '

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Silencing of LASP-1 influences zyxin localization, inhibits proliferation and reduces migration in breast cancer cells

Cited by 106 publications

References 29 publications

Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation

Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation

Ectopic expression of LIM‐nebulette (LASP2) reveals roles in cell migration and spreading

Cytoplasmic Ig‐domain proteins: Cytoskeletal regulators with a role in human disease

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