Studies on effects of KLEIP on cancer-progression

Kelch-like ECT2-interacting protein（KLEIP）是Kelch相关肌动蛋白结合蛋白的成员，最初是作为ECT2癌蛋白的结合伴侣分离的。ECT2是Rho家族小GTP酶的鸟嘌呤核苷酸交换因子，也是胞质分裂的关键调节因子。KLEIP参与MDCK细胞中细胞-细胞粘附位点的肌动蛋白组装。KLEIP还控制血管内皮生长因子诱导的内皮迁移和出芽血管生成。因此，KLEIP似乎在各种情况下具有不同的功能。由于某些kelch相关蛋白与癌细胞有一定的关系，且KLEIP可与ECT2相互作用，因此KLEIP可能参与了肿瘤的发生。在本研究中，我们发现KLEIP在培养的尿路上皮细胞中定位于高尔基复合体，表明KLEIP是一种新的跨高尔基体网络相关蛋白。接下来，我们检测了71个可用标本中的KLEIP表达水平，包括8个正常上皮细胞和63个移行细胞癌（TCC）。8例正常上皮细胞中有5例观察到KLEIP表达，63例TCC中有49例观察到KLEIP表达。KLEIP表达的强度在样品之间变化。进一步分析表明KLEIP的表达强度与肿瘤分级相关，而与T分期无关。因此，KLEIP可能代表尿路上皮癌的新生物标志物。

Kelch-like ECT2-interacting protein (KLEIP) is a member of the kelch-related actin-binding proteins and was originally isolated as a binding partner of the ECT2 oncoprotein. ECT2 is a guanine nucleotide exchange factor for the Rho family of small GTPases, and is also a critical regulator of cytokinesis. KLEIP is involved in actin assembly at sites of cell-cell adhesion in MDCK cells. KLEIP also controls vascular endothelial growth factor-induced endothelial migration and sprouting angiogenesis. Therefore, KLEIP seems to have diverse functions in various situations. Since some kelch-related proteins have relationships with cancer cells and KLEIP can interact with ECT2, KLEIP may be involved in carcinogenesis. In this study, we found that KLEIP was localized to the Golgi complex in cultured urothelial cells, indicating that KLEIP is a novel trans-Golgi network- associated protein. Next, we examined the KLEIP expression levels in 71 available specimens, comprising 8 normal epithelial cells and 63 transitional cell carcinomas (TCCs). KLEIP expression was observed in 5 of 8 normal epithelial cells and 49 of 63 TCCs, respectively. The intensity of KLEIP expression varied among the samples. Further analyses indicated that the intensity of KLEIP expression was correlated with the tumor grade, but not with the T stage. Therefore, KLEIP could represent a novel biomarker for urothelial cancer.