Spatial EGFR Dynamics and Metastatic Phenotypes Modulated by Upregulated EphB2 and Src Pathways in Advanced Prostate Cancer

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dc.contributor.authorLiu, Yen-Liang
dc.contributor.authorHorning, Aaron M.
dc.contributor.authorLieberman, Brandon
dc.contributor.authorKim, Mirae
dc.contributor.authorLin, Che-Kuang
dc.contributor.authorHung, Chia-Nung
dc.contributor.authorChou, Chih-Wei
dc.contributor.authorWang, Chiou-Miin
dc.contributor.authorLin, Chun-Lin
dc.contributor.authorKirma, Nameer B.
dc.contributor.authorLiss, Michael A.
dc.contributor.authorVasisht, Rohan
dc.contributor.authorPerillo, Evan P.
dc.contributor.authorBlocher, Katherine
dc.contributor.authorHorng, Hannah
dc.contributor.authorTaverna, Josephine A.
dc.contributor.authorRuan, Jianhua
dc.contributor.authorYankeelov, Thomas E.
dc.contributor.authorDunn, Andrew K.
dc.contributor.authorHuang, Tim H.-M.
dc.contributor.authorYeh, Hsin-Chih
dc.contributor.authorChen, Chun-Liang
dc.date.accessioned2021-04-19T15:17:28Z
dc.date.available2021-04-19T15:17:28Z
dc.date.issued2019-12-01
dc.date.updated2021-04-19T15:17:28Z
dc.description.abstractAdvanced 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.
dc.description.departmentComputer Science
dc.identifierdoi: 10.3390/cancers11121910
dc.identifier.citationCancers 11 (12): 1910 (2019)
dc.identifier.urihttps://hdl.handle.net/20.500.12588/469
dc.rightsAttribution 4.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectprostate cancer
dc.subjectEGFR
dc.subjectEphB2
dc.subjectSrc
dc.subjectepithelial–mesenchymal transition
dc.subjectmetastasis
dc.subjectsingle-particle tracking
dc.subjectdiffusivity
dc.subjectcompartmentalization
dc.subjectactin
dc.subjectendocytosis
dc.titleSpatial EGFR Dynamics and Metastatic Phenotypes Modulated by Upregulated EphB2 and Src Pathways in Advanced Prostate Cancer
dc.typeArticle

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