PHIP drives glioblastoma motility and invasion by regulating the focal adhesion complex.
Actin Cytoskeleton
/ metabolism
Animals
Brain
/ pathology
Brain Neoplasms
/ blood supply
Cell Adhesion
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cohort Studies
Disease Progression
Female
Focal Adhesions
/ pathology
Gene Dosage
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Glioblastoma
/ blood supply
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Intravital Microscopy
Mice
Microscopy, Confocal
Neoplasm Invasiveness
/ genetics
Neovascularization, Pathologic
/ genetics
Time-Lapse Imaging
Vinculin
/ metabolism
Xenograft Model Antitumor Assays
PHIP
angiogenesis
glioblastoma
invasion
motility
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
21 04 2020
21 04 2020
Historique:
pubmed:
11
4
2020
medline:
28
7
2020
entrez:
11
4
2020
Statut:
ppublish
Résumé
The invasive behavior of glioblastoma is essential to its aggressive potential. Here, we show that pleckstrin homology domain interacting protein (PHIP), acting through effects on the force transduction layer of the focal adhesion complex, drives glioblastoma motility and invasion. Immunofluorescence analysis localized PHIP to the leading edge of glioblastoma cells, together with several focal adhesion proteins: vinculin (VCL), talin 1 (TLN1), integrin beta 1 (ITGB1), as well as phosphorylated forms of paxillin (pPXN) and focal adhesion kinase (pFAK). Confocal microscopy specifically localized PHIP to the force transduction layer, together with TLN1 and VCL. Immunoprecipitation revealed a physical interaction between PHIP and VCL. Targeted suppression of PHIP resulted in significant down-regulation of these focal adhesion proteins, along with zyxin (ZYX), and produced profoundly disorganized stress fibers. Live-cell imaging of glioblastoma cells overexpressing a ZYX-GFP construct demonstrated a role for PHIP in regulating focal adhesion dynamics.
Identifiants
pubmed: 32273388
pii: 1914505117
doi: 10.1073/pnas.1914505117
pmc: PMC7183218
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
PHIP protein, human
0
VCL protein, human
0
Vinculin
125361-02-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
9064-9073Subventions
Organisme : NCI NIH HHS
ID : R01 CA114337
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA122947
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226802
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA175768
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA215755
Pays : United States
Déclaration de conflit d'intérêts
Competing interest statement: C.C. and J.D.L. are coauthors on a 2018 research article.
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