EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis.
dc.contributor.author | Feng, Haizhong | |
dc.contributor.author | Lopez, Giselle Y | |
dc.contributor.author | Kim, Chung Kwon | |
dc.contributor.author | Alvarez, Angel | |
dc.contributor.author | Duncan, Christopher G | |
dc.contributor.author | Nishikawa, Ryo | |
dc.contributor.author | Nagane, Motoo | |
dc.contributor.author | Su, An-Jey A | |
dc.contributor.author | Auron, Philip E | |
dc.contributor.author | Hedberg, Matthew L | |
dc.contributor.author | Wang, Lin | |
dc.contributor.author | Raizer, Jeffery J | |
dc.contributor.author | Kessler, John A | |
dc.contributor.author | Parsa, Andrew T | |
dc.contributor.author | Gao, Wei-Qiang | |
dc.contributor.author | Kim, Sung-Hak | |
dc.contributor.author | Minata, Mutsuko | |
dc.contributor.author | Nakano, Ichiro | |
dc.contributor.author | Grandis, Jennifer R | |
dc.contributor.author | McLendon, Roger E | |
dc.contributor.author | Bigner, Darell D | |
dc.contributor.author | Lin, Hui-Kuan | |
dc.contributor.author | Furnari, Frank B | |
dc.contributor.author | Cavenee, Webster K | |
dc.contributor.author | Hu, Bo | |
dc.contributor.author | Yan, Hai | |
dc.contributor.author | Cheng, Shi-Yuan | |
dc.date.accessioned | 2019-01-02T22:36:49Z | |
dc.date.available | 2019-01-02T22:36:49Z | |
dc.date.issued | 2014-09 | |
dc.date.updated | 2019-01-02T22:36:46Z | |
dc.description.abstract | Aberrant activation of EGFR in human cancers promotes tumorigenesis through stimulation of AKT signaling. Here, we determined that the discoidina neuropilin-like membrane protein DCBLD2 is upregulated in clinical specimens of glioblastomas and head and neck cancers (HNCs) and is required for EGFR-stimulated tumorigenesis. In multiple cancer cell lines, EGFR activated phosphorylation of tyrosine 750 (Y750) of DCBLD2, which is located within a recently identified binding motif for TNF receptor-associated factor 6 (TRAF6). Consequently, phosphorylation of DCBLD2 Y750 recruited TRAF6, leading to increased TRAF6 E3 ubiquitin ligase activity and subsequent activation of AKT, thereby enhancing EGFR-driven tumorigenesis. Moreover, evaluation of patient samples of gliomas and HNCs revealed an association among EGFR activation, DCBLD2 phosphorylation, and poor prognoses. Together, our findings uncover a pathway in which DCBLD2 functions as a signal relay for oncogenic EGFR signaling to promote tumorigenesis and suggest DCBLD2 and TRAF6 as potential therapeutic targets for human cancers that are associated with EGFR activation. | |
dc.identifier | 73093 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.issn | 1558-8238 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | American Society for Clinical Investigation | |
dc.relation.ispartof | The Journal of clinical investigation | |
dc.relation.isversionof | 10.1172/jci73093 | |
dc.subject | Cells, Cultured | |
dc.subject | Humans | |
dc.subject | Glioma | |
dc.subject | Head and Neck Neoplasms | |
dc.subject | Brain Neoplasms | |
dc.subject | Receptor, Epidermal Growth Factor | |
dc.subject | TNF Receptor-Associated Factor 6 | |
dc.subject | Membrane Proteins | |
dc.subject | Signal Transduction | |
dc.subject | Phosphorylation | |
dc.subject | Proto-Oncogene Proteins c-akt | |
dc.subject | Carcinogenesis | |
dc.title | EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis. | |
dc.type | Journal article | |
duke.contributor.orcid | Lopez, Giselle Y|0000-0001-5435-6668 | |
duke.contributor.orcid | McLendon, Roger E|0000-0001-6682-4588 | |
duke.contributor.orcid | Bigner, Darell D|0000-0001-5548-4899 | |
pubs.begin-page | 3741 | |
pubs.end-page | 3756 | |
pubs.issue | 9 | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Pathology | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Surgery | |
pubs.organisational-group | Neurosurgery | |
pubs.organisational-group | Pharmacology & Cancer Biology | |
pubs.organisational-group | Basic Science Departments | |
pubs.publication-status | Published | |
pubs.volume | 124 |