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@ARTICLE{Tran:289597,
author = {C. S. Tran and J. Kersten and J. Yan and M. Breinig$^*$ and
T. Huth and T. Poth and O. Colasanti and T. Riedl$^*$ and S.
Faure-Dupuy and S. Diehl and L. Verhoye and T.-F. Li and M.
Lingemann and P. Schult and G. Ahlén and L. Frelin and F.
Kühnel and F. W. R. Vondran and K. Breuhahn and P. Meuleman
and M. Heikenwälder and P. Schirmacher and R.
Bartenschlager$^*$ and V. Laketa and S. Roessler and D. F.
Tschaharganeh$^*$ and M. Sällberg and V. Lohmann},
title = {{P}hosphatidylinositol 4-kinase {III} alpha governs
cytoskeletal organization for invasiveness of liver cancer
cells.},
journal = {Gastroenterology},
volume = {167},
number = {3},
issn = {0016-5085},
address = {Philadelphia, Pa. [u.a.]},
publisher = {Saunders},
reportid = {DKFZ-2024-00830},
pages = {522-537},
year = {2024},
note = {2024 Aug;167(3):522-537},
abstract = {High expression of phosphatidylinositol 4-kinase III alpha
(PI4KIIIα) correlates with poor survival rates in patients
with hepatocellular carcinoma (HCC). In addition, Hepatitis
C virus (HCV) infections activate PI4KIIIα and contribute
to HCC progression. We aimed at mechanistically
understanding the impact of PI4KIIIα on the progression of
liver cancer and the potential contribution of HCV in this
process.Several hepatic cell culture and mouse models were
used to study functional importance of PI4KIIIα on liver
pathogenesis. Antibody arrays, gene silencing and PI4KIIIα
specific inhibitor were applied to identify the involved
signaling pathways. The contribution of HCV was examined by
using HCV infection or overexpression of its nonstructural
protein.High PI4KIIIα expression and/or activity induced
cytoskeletal rearrangements via increased-phosphorylation of
paxillin and cofilin. This led to morphological alterations
and higher migratory and invasive properties of liver cancer
cells. We further identified the liver specific lipid kinase
phosphatidylinositol 3-kinase C2 domain-containing subunit
gamma (PIK3C2γ) working downstream of PI4KIIIα in
regulation of the cytoskeleton. PIK3C2γ generates plasma
membrane (PM) phosphatidylinositol 3,4-bisphosphate
[PI(3,4)P2]-enriched, invadopodia-like structures which
regulate cytoskeletal reorganization by promoting Akt2
phosphorylation.PI4KIIIα regulates cytoskeleton
organization via PIK3C2γ/Akt2/paxillin-cofilin to favor
migration and invasion of liver cancer cells. These findings
provide mechanistic insight into the contribution of
PI4KIIIα and HCV to progression of liver cancer and
identify promising targets for therapeutic intervention.},
keywords = {Akt2 (Other) / HCV (Other) / PIK3C2G (Other) /
hepatocellular carcinoma (Other) / phospholipid (Other)},
cin = {F190 / F180 / D440 / F170 / D430},
ddc = {610},
cid = {I:(DE-He78)F190-20160331 / I:(DE-He78)F180-20160331 /
I:(DE-He78)D440-20160331 / I:(DE-He78)F170-20160331 /
I:(DE-He78)D430-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38636680},
doi = {10.1053/j.gastro.2024.04.009},
url = {https://inrepo02.dkfz.de/record/289597},
}