Show simple item record

dc.contributor.authorBartel, Karin
dc.contributor.authorWinzi, Maria
dc.contributor.authorUlrich, Melanie
dc.contributor.authorKoeberle, Andreas
dc.contributor.authorMenche, Dirk
dc.contributor.authorWerz, Oliver
dc.contributor.authorMüller, Rolf
dc.contributor.authorGuck, Jochen
dc.contributor.authorVollmar, Angelika M
dc.contributor.authorvon Schwarzenberg, Karin
dc.date.accessioned2017-09-05T13:22:21Z
dc.date.available2017-09-05T13:22:21Z
dc.date.issued2017-02-07
dc.identifier.citationV-ATPase inhibition increases cancer cell stiffness and blocks membrane related Ras signaling - a new option for HCC therapy. 2017, 8 (6):9476-9487 Oncotargeten
dc.identifier.issn1949-2553
dc.identifier.pmid28036299
dc.identifier.doi10.18632/oncotarget.14339
dc.identifier.urihttp://hdl.handle.net/10033/621092
dc.description.abstractHepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide and the third leading cause of cancer-related death. However, therapy options are limited leaving an urgent need to develop new strategies. Currently, targeting cancer cell lipid and cholesterol metabolism is gaining interest especially regarding HCC. High cholesterol levels support proliferation, membrane-related mitogenic signaling and increase cell softness, leading to tumor progression, malignancy and invasive potential. However, effective ways to target cholesterol metabolism for cancer therapy are still missing. The V-ATPase inhibitor archazolid was recently shown to interfere with cholesterol metabolism. In our study, we report a novel therapeutic potential of V-ATPase inhibition in HCC by altering the mechanical phenotype of cancer cells leading to reduced proliferative signaling. Archazolid causes cellular depletion of free cholesterol leading to an increase in cell stiffness and membrane polarity of cancer cells, while hepatocytes remain unaffected. The altered membrane composition decreases membrane fluidity and leads to an inhibition of membrane-related Ras signaling resulting decreased proliferation in vitro and in vivo. V-ATPase inhibition represents a novel link between cell biophysical properties and proliferative signaling selectively in malignant HCC cells, providing the basis for an attractive and innovative strategy against HCC.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleV-ATPase inhibition increases cancer cell stiffness and blocks membrane related Ras signaling - a new option for HCC therapy.en
dc.typeArticleen
dc.contributor.departmentHIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus E8.1, 66123 Saarbrücken, Germany.en
dc.identifier.journalOncotargeten
refterms.dateFOA2018-06-13T04:00:35Z
html.description.abstractHepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide and the third leading cause of cancer-related death. However, therapy options are limited leaving an urgent need to develop new strategies. Currently, targeting cancer cell lipid and cholesterol metabolism is gaining interest especially regarding HCC. High cholesterol levels support proliferation, membrane-related mitogenic signaling and increase cell softness, leading to tumor progression, malignancy and invasive potential. However, effective ways to target cholesterol metabolism for cancer therapy are still missing. The V-ATPase inhibitor archazolid was recently shown to interfere with cholesterol metabolism. In our study, we report a novel therapeutic potential of V-ATPase inhibition in HCC by altering the mechanical phenotype of cancer cells leading to reduced proliferative signaling. Archazolid causes cellular depletion of free cholesterol leading to an increase in cell stiffness and membrane polarity of cancer cells, while hepatocytes remain unaffected. The altered membrane composition decreases membrane fluidity and leads to an inhibition of membrane-related Ras signaling resulting decreased proliferation in vitro and in vivo. V-ATPase inhibition represents a novel link between cell biophysical properties and proliferative signaling selectively in malignant HCC cells, providing the basis for an attractive and innovative strategy against HCC.


Files in this item

Thumbnail
Name:
Bartel et al.pdf
Size:
5.141Mb
Format:
PDF
Description:
Open Access publication
Thumbnail
Name:
supplementary files.pdf
Size:
2.441Mb
Format:
PDF
Description:
supplementary materials

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by-nc-sa/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/