STAP-2 protein promotes prostate cancer growth by enhancing epidermal growth factor receptor stabilization.
Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of STAP-2 to the behavior of other types of cancer cells is unclear. Here, we show that STAP-2 promotes tumorigenesis of prostate cancer ... cells through up-regulation of EGF receptor (EGFR) signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown. EGF-induced gene expression and phosphorylation of AKT, ERK, and STAT3 were significantly decreased in STAP-2-knockdown DU145 cells. Mechanistically, we found that STAP-2 interacted with EGFR and enhanced its stability by inhibiting c-CBL-mediated EGFR ubiquitination. Our results indicate that STAP-2 promotes prostate cancer progression via facilitating EGFR activation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Proliferation, Humans, Male, Mice, Inbred BALB C, Phosphoproteins, Phosphorylation, Prostatic Neoplasms, Protein Stability, Receptor, Epidermal Growth Factor, Signal Transduction, Tumor Cells, Cultured, Ubiquitination, Xenograft Model Antitumor Assays
Adaptor Proteins, Signal Transducing, Animals, Cell Proliferation, Humans, Male, Mice, Inbred BALB C, Phosphoproteins, Phosphorylation, Prostatic Neoplasms, Protein Stability, Receptor, Epidermal Growth Factor, Signal Transduction, Tumor Cells, Cultured, Ubiquitination, Xenograft Model Antitumor Assays
J. Biol. Chem.
Date: Dec. 24, 2016
PubMed ID: 28986450
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