大量研究表明前列腺癌中EGFR信号通路异常激活，该信号通路激活主要是由EGFR突变或高表达造成的，临床研究表明与EGFR突变相比EGFR高表达的频率更高，且这种高表达与基因拷贝数增加无关，提示EGFR蛋白降解受阻可能是前列腺癌中EGFR信号通路异常激活的主要原因。发现新的影响EGFR蛋白降解的调控因子，对揭示前列腺癌进展有重要意义。本课题组前期研究证明SGEF是一种可能的癌基因，但SGEF在前列腺癌中发挥作用的分子机制尚不明确。我们最近的研究表明在前列腺癌中敲低SGEF表达可通过溶酶体途径促进EGFR降解，但SGEF如何调控EGFR的降解、SGEF调控EGFR稳定性与GEF活性的相关性、协同SGEF调控EGFR稳定性的分子，以及SGEF增强EGFR蛋白稳定性在前列腺癌进展中的作用并不明确。本课题拟针对上述问题开展研究，研究结果将为揭示前列腺癌进展的分子机制提供新线索。

A number of experimental and clinical studies have implicated abnormality activation of EGFR signal pathway in prostate tumorigenesis. Studies on a series of prostate adenocarcinomas revealed that EGFR overexpression was the most frequent EGFR related abnormality while EGFR mutation was a minor event. Moreover, there was no correlation between gene copy number and EGFR protein expression suggesting that EGFR overexpression in prostate cancer may be primarily due to the deregulation of EGFR degradation. Previously we demonstrated an elevated 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. A recently study from our lab demonstrated that knockdown SGEF expression in various prostate cancer cells promote EGFR degradation through lysosome pathway. In this project , we are going to further study : how SGEF inhibite EGFR degradation, if SGEF modulated EGFR protein stability is involve its GEFs （Guanine Nucleotide Exchange Factor，GEFs） activity, what are the moleculars that involed in SGEF modulating EGFR protein stability, and the role of SGEF increase EGFR protein stability in prostate cancer progression. The result of this study may provide an novel clue to reveal the molecular mechanism of prostate cancer progression.