SALL4与FOXM1相互作用通过调控经血干细胞上皮间质转化反应影响子宫内膜异位症恶变的机制研究

SALL4是新发现的原癌基因，其作用机制尚不清楚。我们在国内外首次报道SALL4具有促进子宫内膜癌细胞增殖侵袭能力。前期研究从内异症相关卵巢癌患者经血干细胞基因差异表达谱出发，发现SALL4基因在恶性患者经血干细胞中表达强度高于健康女性以及内异症患者。SALL4具有诱导经血干细胞恶性分化潜能，促进恶变后癌细胞增殖侵袭等作用。其原因可能与SALL4转录后与FOXM1蛋白相互作用通过下游ß-Catenin/TCF通路诱导经血干细胞EMT反应有关。结合前期基础，通过体内外实验研究SALL4与FOXM1相互作用及其下游信号通路活化是否通过激活经血干细胞EMT反应促进干细胞恶性分化潜能，促进癌细胞增殖，迁移及侵袭能力。针对SALL4与FOXM1结构域，设计小分子肽，探索内异症恶变潜在治疗靶点，为进一步认识内异症恶变病因，临床疾病预防、诊断及治疗提供理论依据和基础。

SALL4 is a newly found oncogene, its mechanism remained unclear. We firstly reported that SALL4, expressed in endometrial cancers, promoted cell proliferation and invasion. The results of our previously study about gene arrays in MBSC of endometriosis associated ovarian carcinoma (EAOEC) showed that SALL4 was highly expressed in MBSC of EAOEC as compared with it in endomtiral patients. SALL4 may promote EMSC to lead to malignant transformation and promote malignant cell proliferation and invasion. It might be related that SALL4 interacted with FOXM1 and then promoted EMT reaction of MBSC through activating ß-Catenin/TCF signal pathway. According to these results, we planned to study the mechanism of SALL4 in the malignant transformation of MBSC and the proliferation and invasion of EAOEC. To testify whether or not the mechanism of SALL4 and FOXM1 interation is related to promoted EMT reaction of MBSC through activating ß-Catenin/TCF signal pathway. We designed one novel peptides that could block SALL4 domain. It will help us find the treatment target of malignant transformation of endometriosis. The results of our study will play an important role in exploring the etiology of malignant transformation as well as providing the theoretical evidence to clinical diagnosis and treatment.