CD151 Promotes Cell Metastasis Via Activating TGF-?1/Smad Signaling In Renal Cell Carcinoma

Objective: Tetraspanin CD151 has been identified as a tumor promoter,which is upregulated in different malignant cell types.Nonetheless,the role of CD151 and its inherent mechanism in renal cell carcinoma(RCC)is still to be explored.The goal of this study was to ascertain the expression level of CD151 in RCC and delve its function in RCC cell lines.Methods: Quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting(WB)were used to examine the CD151 expression levels in RCC samples and RCC cell lines.After RCC cells being stably transfected with lentivirus,a series of in vitro assays including transwell migration and invasion assays were conducted to figure out the relationship between CD151 and RCC.To further investigate how CD151 promotes cell migration and invasion by targeting TGF-?1,a number of hallmarks of EMT and TGF-?1/Smad signaling were detected and a rescue experiment was performed.Additionally,tissue microarrays(TMAs)of RCC samples and immunohistochemistry(IHC)analyses were applied to evaluate the correlation between the expression of CD151 and clinicopathologic characteristics of RCC patients.Results: The outcomes of Western Blot and qRT-PCR revealed that CD151 was meaningfully overexpressed in RCC cell lines and tissues.Besides,cell function experiment in Caki-1 and Caki-2 pointed that cell migration and invasion capacities in CD151 knockdown group were suppressed compared with the negative control group,while CD151 overexpression group displayed the contrary results.Mechanism study revealed a significant decrease of E-cadherin and increase of TGF-?1,Smad2/3,p-Smad2,p-Smad3,N-cadherin,vimentin and MMP-9 in CD151 over-expressed group,while the results were contrary in CD151 knockdown group.According to analysis of TMAs and IHC,advanced tumor stage and poor survival were significantly associated with high CD151 level(p < 0.05).Nevertheless,no significant differences were revealed between age,gender,tumor size,histological grade and expression of CD151.Conclusion: Our results indicated that CD151 is upregulated in RCC and high level of CD151 is associated with advanced tumor stage and poor survival significantly.In addition,CD151 might exhibit a prominent role in migration and invasion of RCC cells via activating TGF-?1/Smad signaling pathway.Consequently,CD151 might serve as a potential biomarker for the diagnosis,treatment and prognosis of RCC.