前期我们将SLP2作为候选癌基因发现其在胃癌组织中表达升高且与患者预后不良相关，但其调控机制尚不清楚。前期工作中，我们通过酵母双杂交筛选得到相互作用蛋白PHB，发现沉默SLP2可促进PHB泛素化降解并抑制MAPK信号通路激活。此外，在胃癌细胞中导入外源性SLP2可促进内源性SLP2的表达，提示SLP2可能存在自身正反馈调控。分析发现SLP2启动子区域存在MAPK信号通路下游分子ELK1的结合位点。由此我们提出一个正反馈调控环路的设想：SLP2可通过抑制PHB泛素化降解活化MAPK信号通路进而促进ELK1对SLP2的转录。为验证该设想，我们拟进一步证明：一、SLP2通过与PHB相互结合抑制其泛素化降解；二、SLP2与PHB相互作用活化MAPK信号通路，从而诱导ELK1激活；三、转录因子ELK1促进SLP2的转录。该项目的顺利完成有利于提高对SLP2参与胃癌细胞增殖和转移的重要调控机制的认识。

SLP2 was previously screened as a potential oncogene and proved to be up-regulated and associated with poor prognosis in patients with gastric cancer. However, the certain mechanism of SLP2 in gastric cancer is still unclear. To address this issue, PHB was selected to potentially interact with SLP2 using a yeast two-hybrid system. Moreover, we noticed that degradation of PHB by ubiquitination and inhibition of MAPK signaling pathway was prompted in SLP2-silenced cells. In addition, the endogenous SLP2 was elevated when the exogenous SLP2 was transfected, which indicated a potential positive feedback loop of SLP2. Interestingly, we also found that there were binding sites of ELK1, as a downstream transcript factor of MAPK signaling pathway, in the promoter region of SLP2. Therefore, we propose the hypothesis of the positive feedback loop: SLP2 might activate the MAPK signaling pathway and further promote transcriptional activity of ELK1 through the inhibited degradation of PHB ubiquitination. We designed the following studies to verify the hypothesis: first, the interaction of SLP2 and PHB could decrease the degradation of PHB by ubiquitination. Second, the interaction of SLP2 and PHB could activate MAPK signaling pathway and then induce the activation of ELK1. Lastly, ELK1 was potential to stimulate the transcription of SLP2. The study will greatly promotes our recognition on the regulatory mechanism of SLP2 in the proliferation and metastasis of gastric cancer.