Strong fascin expression promotes metastasis independent of its F-actin bundling activity
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Strong fascin expression promotes metastasis independent of its F-actin bundling activity. / Heinz, Lisa S; Muhs, Stefanie; Schiewek, Johanna; Grüb, Saskia; Nalaskowski, Marcus; Lin, Yuan-Na; Wikman, Harriet; Oliveira-Ferrer, Leticia; Lange, Tobias; Wellbrock, Jasmin; Konietzny, Anja; Mikhaylova, Marina; Windhorst, Sabine.
In: ONCOTARGET, Vol. 8, No. 66, 15.12.2017, p. 110077-110091.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Strong fascin expression promotes metastasis independent of its F-actin bundling activity
AU - Heinz, Lisa S
AU - Muhs, Stefanie
AU - Schiewek, Johanna
AU - Grüb, Saskia
AU - Nalaskowski, Marcus
AU - Lin, Yuan-Na
AU - Wikman, Harriet
AU - Oliveira-Ferrer, Leticia
AU - Lange, Tobias
AU - Wellbrock, Jasmin
AU - Konietzny, Anja
AU - Mikhaylova, Marina
AU - Windhorst, Sabine
PY - 2017/12/15
Y1 - 2017/12/15
N2 - High expression of the actin bundling protein Fascin increases the malignancy of tumor cells. Here we show that fascin expression is up-regulated in more malignant sub-cell lines of MDA-MB-231 cells as compared to parental cells. Since also parental MDA-MB-231 cells exhibit high fascin levels, increased fascin expression was termed as "hyperexpression". To examine the effect of fascin hyperexpression, fascin was hyperexpressed in parental MDA-MB-231 cells and metastasis was analyzed in NOD scid gamma (NSG) mice. In addition, the effect of fascin mutants with inactive or constitutively active actin bundling activity was examined. Unexpectedly, we found that hyperexpression of both, wildtype (wt) and mutant fascin strongly increased metastasis in vivo, showing that the effect of fascin hyperexpression did not depend on its actin bundling activity. Cellular assays revealed that hyperexpression of wt and mutant fascin increased adhesion of MDA-MB-231 cells while transmigration and proliferation were not affected. Since it has been shown that fascin controls adhesion by directly interacting with microtubules (MTs), we analyzed if fascin hyperexpression affects MT dynamics. We found that at high concentrations fascin significantly increased MT dynamics in cells and in cell-free approaches. In summary our data show that strong expression of fascin in breast cancer cells increases metastasis independent of its actin bundling activity. Thus, it seems that the mechanism of fascin-stimulated metastasis depends on its concentration.
AB - High expression of the actin bundling protein Fascin increases the malignancy of tumor cells. Here we show that fascin expression is up-regulated in more malignant sub-cell lines of MDA-MB-231 cells as compared to parental cells. Since also parental MDA-MB-231 cells exhibit high fascin levels, increased fascin expression was termed as "hyperexpression". To examine the effect of fascin hyperexpression, fascin was hyperexpressed in parental MDA-MB-231 cells and metastasis was analyzed in NOD scid gamma (NSG) mice. In addition, the effect of fascin mutants with inactive or constitutively active actin bundling activity was examined. Unexpectedly, we found that hyperexpression of both, wildtype (wt) and mutant fascin strongly increased metastasis in vivo, showing that the effect of fascin hyperexpression did not depend on its actin bundling activity. Cellular assays revealed that hyperexpression of wt and mutant fascin increased adhesion of MDA-MB-231 cells while transmigration and proliferation were not affected. Since it has been shown that fascin controls adhesion by directly interacting with microtubules (MTs), we analyzed if fascin hyperexpression affects MT dynamics. We found that at high concentrations fascin significantly increased MT dynamics in cells and in cell-free approaches. In summary our data show that strong expression of fascin in breast cancer cells increases metastasis independent of its actin bundling activity. Thus, it seems that the mechanism of fascin-stimulated metastasis depends on its concentration.
KW - Journal Article
U2 - 10.18632/oncotarget.22249
DO - 10.18632/oncotarget.22249
M3 - SCORING: Journal article
C2 - 29299131
VL - 8
SP - 110077
EP - 110091
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 66
ER -