Abstract
The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that downregulated in various malignant cell types. However, the function of CD82 and its underlying anti-metastasis role in renal cell carcinoma (RCC) is still unraveled. Here, we investigated the expression of CD82 in RCC and explored its regulatory mechanism in RCC cell lines. We found that CD82 was down-regulated in RCC tissues and cells and its expression was significantly associated with histological grade(p=0.041), tumour stage (p=0.036) and tumor size(p=0.020) by analyzing tissue microarrays. After upregulation of CD82 through lentivirus, reduced ability of migration and invasion in Caki-1 cells were detected. In contrast, gene silencing of CD82 by small interfering RNA promoted metastatic and invasive potential of 786-O cells. Furthermore, Western blot was performed to identify the influence of CD82 on MMP family and TGF-β1/Smad pathway in RCC. Subsequently, upregulating protein level of TGF-β1 with the overexpression of CD82 could rescue the malignant behaviors inhibited by CD82 which indicated that CD82 played its inhibitory role in RCC partially by attenuating the expression of TGF-β1. Taken together, CD82 played a prominent role in migration and invasion of RCC cells and it might exhibit its inhibitory role in RCC metastasis via block TGF-β1/Smad signaling pathway.
Highlights
Kidney cancer is one of the top 10 most common cancers in the world and renal cell carcinoma (RCC) accounts for 85% of all renal malignancies with an incidence that continues to rise
CD82 played a prominent role in migration and invasion of RCC cells and it might exhibit its inhibitory role in RCC metastasis via block TGF-β1/Smad signaling pathway
The results showed that CD82 was significantly down-regulated in RCC tissues, compared with adjacent normal tissues (p
Summary
Kidney cancer is one of the top 10 most common cancers in the world and renal cell carcinoma (RCC) accounts for 85% of all renal malignancies with an incidence that continues to rise. Exploring potential molecular mechanisms and identifying new therapeutic targets are becoming extremely necessary for RCC clinical treatment. Recent www.impactjournals.com/oncotarget years studies have demonstrated CD82 as a metastatic suppressor in many malignant solid cancer cell types including prostate cancer [9],bladder cancer [10], breast cancer [11], pancreatic cancer, and hepatocarcinoma [12] cells. To investigated the potential of CD82 on RCC metastasis in RCC cells, lentiviral vector and small interfering RNAs (siRNAs) were used to overexpress or silence CD82 in RCC cell lines. What’s more, we found the TGF-β1 pathway was involved in the metastasis of RCC cell lines. The following results may revealed how CD82 act as a tumor suppressor in RCC cell lines and provide a potential biomarker for treatment of RCC
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