Cullin 4B (CUL4B), encoding a scaffold protein in Cullin RING ubiquitin-ligase complexes (CRL4B), is overexpressed and serves as an oncogene in various solid tumors. However, the roles and the underlying mechanisms of CUL4B in renal cell carcinoma (RCC) are still unknown. In this study, we demonstrated that CUL4B was significantly upregulated in RCC cells and clinical specimens, and its overexpression was correlated with poor survival of RCC patients. Knockdown of CUL4B resulted in the inhibition of proliferation, migration and invasion of RCC cells. Furthermore, we found that the expression of CUL4B is positively correlated with c-Met expression in RCC cells and tissues. Konckdown of c-Met or treatment with c-Met inhibitor, SU11274, could block the increase in cell proliferation, migration and invasion induced by CUL4B-overexpression. We also showed that CUL4B overexpression significantly accelerated xenograft tumor growth, and administration of SU11274 could also abrogate the accelerated tumor growth induced by CUL4B overexpression in vivo. These findings shed light on the contribution of CUL4B to tumorigenesis in RCC via activating c-Met signaling and its therapeutic implications in RCC patients.

Cullin 4B (CUL4B) 在 Cullin RING 泛素连接酶复合物 (CRL4B) 中编码支架蛋白，在各种实体瘤中过表达并作为致癌基因。然而，CUL4B 在肾细胞癌 (RCC) 中的作用和潜在机制仍不清楚。在这项研究中，我们证明了 CUL4B 在 RCC 细胞和临床标本中显着上调，其过表达与 RCC 患者的不良生存相关。CUL4B 的敲低导致 RCC 细胞增殖、迁移和侵袭的抑制。此外，我们发现 CUL4B 的表达与 RCC 细胞和组织中的 c-Met 表达呈正相关。抑制 c-Met 或用 c-Met 抑制剂 SU11274 处理可以阻断 CUL4B 过表达诱导的细胞增殖、迁移和侵袭的增加。体内。这些发现阐明了 CUL4B通过激活 c-Met 信号传导对 RCC 肿瘤发生的贡献及其对 RCC 患者的治疗意义。