Spatial EGFR Dynamics and Metastatic Phenotypes Modulated by Upregulated EphB2 and Src Pathways in Advanced Prostate Cancer.
EGFR
EphB2
Src
actin
compartmentalization
diffusivity
endocytosis
epithelial–mesenchymal transition
metastasis
prostate cancer
single-particle tracking
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
01 Dec 2019
01 Dec 2019
Historique:
received:
04
11
2019
revised:
23
11
2019
accepted:
26
11
2019
entrez:
7
12
2019
pubmed:
7
12
2019
medline:
7
12
2019
Statut:
epublish
Résumé
Advanced prostate cancer is a very heterogeneous disease reflecting in diverse regulations of oncogenic signaling pathways. Aberrant spatial dynamics of epidermal growth factor receptor (EGFR) promote their dimerization and clustering, leading to constitutive activation in oncogenesis. The EphB2 and Src signaling pathways are associated with the reorganization of the cytoskeleton leading to malignancy, but their roles in regulating EGFR dynamics and activation are scarcely reported. Using single-particle tracking techniques, we found that highly phosphorylated EGFR in the advanced prostate cancer cell line, PC3, was associated with higher EGFR diffusivity, as compared with LNCaP and less aggressive DU145. The increased EGFR activation and biophysical dynamics were consistent with high proliferation, migration, and invasion. After performing single-cell RNA-seq on prostate cancer cell lines and circulating tumor cells from patients, we identified that upregulated gene expression in the EphB2 and Src pathways are associated with advanced malignancy. After dasatinib treatment or siRNA knockdowns of EphB2 or Src, the PC3 cells exhibited significantly lower EGFR dynamics, cell motility, and invasion. Partial inhibitory effects were also found in DU145 cells. The upregulation of parts of the EphB2 and Src pathways also predicts poor prognosis in the prostate cancer patient cohort of The Cancer Genome Atlas. Our results provide evidence that overexpression of the EphB2 and Src signaling pathways regulate EGFR dynamics and cellular aggressiveness in some advanced prostate cancer cells.
Identifiants
pubmed: 31805710
pii: cancers11121910
doi: 10.3390/cancers11121910
pmc: PMC6966510
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002646
Pays : United States
Organisme : Cancer Prevention and Research Institute of Texas
ID : RP150600
Organisme : Cancer Prevention and Research Institute of Texas
ID : RR160005
Organisme : National Institutes of Health (USA)
ID : T32CA148724
Organisme : National Institutes of Health (USA)
ID : CA193038
Organisme : National Institutes of Health (USA)
ID : U54CA217297
Organisme : NCI NIH HHS
ID : R21 CA193038
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA148724
Pays : United States
Organisme : Robert A. Welch Foundation
ID : F-1833
Organisme : National Institutes of Health (USA)
ID : P30CA054174
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
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