SGEF enhances EGFR stability through delayed EGFR trafficking from early to late endosomes
SGEF enhances EGFR stability through delayed EGFR trafficking from early to late endosomes
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SGEF 通过延迟 EGFR 从早期内体到晚期内体的运输来增强 EGFR 稳定性。
DOI：
10.1093/carcin/bgt157
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发表时间：
2013-09-01
期刊：
影响因子：
4.7
通讯作者：
Zhou, Jianguang
中科院分区：
文献类型：
--
作者：
Wang, Hongtao;Li, Shanhu;Zhou, Jianguang
在此之前，我们在前列腺癌的临床标本中证实了含有SH3的鸟核苷酸交换因子(Sgef)的高表达，并暗示了Sgef在前列腺癌发生中的作用。然而，SGF调节前列腺癌发生的分子机制尚不清楚。在这项研究中，我们发现Sgef的表达延缓了前列腺癌细胞中表皮生长因子受体(EGFR)的降解，并且不依赖于其鸟核苷酸交换因子(Gef)的功能。我们进一步表明，这种延迟的降解是由于EGFR从早期到晚期内含体转运的延迟，而不是由于EGFR泛素化的减少。最后，我们的研究结果表明，在前列腺癌细胞中，缺失表皮生长因子显著抑制了由表皮生长因子诱导的EGFR信号级联反应和细胞迁移。我们首次报道了一种针对RhoG的Sgef功能，该功能排除了gef和sgef通过延迟其溶酶体的分选和降解来增强EGFR的稳定性和信号转导的能力。这可能是SEF促进前列腺癌进展的机制之一。
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.