title: SGEF enhances EGFR stability through delayed EGFR trafficking from early to late endosomes.
abstract: Previously, we demonstrated an elevated SH3-containing guanine nucleotide exchange factor (SGEF) expression in clinical specimens with prostate cancer and implicated the role of SGEF in prostate tumorigenesis. However, the molecular mechanism behind the SGEF regulation of prostate cancer development is not known. In this study, we show that SGEF expression delays epidermal growth factor receptor (EGFR) degradation in prostate cancer cells and is independent from its guanine nucleotide exchange factor (GEF) function. We further show that the delayed degradation is due to a delay in EGFR trafficking from early to late endosomes and not to a decrease in EGFR ubiquitination. Finally, we show that depletion of SGEF significantly inhibits epidermal growth factor-induced EGFR signaling cascade and cell migration in the prostate cancer cells. We report for the first time an SGEF function for RhoG that excludes GEF and the ability of SGEF to enhance EGFR stability and signaling by delaying its lysosomal sorting and degradation. This could be one mechanism by which SGEF contributes to prostate cancer progression.
authors: Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Taiping Road, Haidian, Beijing 100850, China and.
authors: Hongtao
authors: H
authors: Wang
authors: Shanhu
authors: S
authors: Li
authors: Hailiang
authors: H
authors: Li
authors: Changling
authors: C
authors: Li
authors: Kaopeng
authors: K
authors: Guan
authors: Guolan
authors: G
authors: Luo
authors: Lan
authors: L
authors: Yu
authors: Ruiqin
authors: R
authors: Wu
authors: Xiaoqing
authors: X
authors: Zhang
authors: Jian
authors: J
authors: Wang
authors: Jianguang
authors: J
authors: Zhou
mesh_terms: D063646:Carcinogenesis; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms; D059748:Proteolysis
chemical_list: C473930:ARHGEF26 protein, human; D020662:Guanine Nucleotide Exchange Factors; C512478:EGFR protein, human; D066246:ErbB Receptors