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High-Level S100A6 Promotes Metastasis and Predicts the Outcome of T1–T2 Stage in Clear Cell Renal Cell Carcinoma

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Abstract

S100A6 (calcyclin), functions in cell cycle progression and differentiation, has been reported to promote the tumorigenesis and malignancy of many types of cancers. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC, lacking both promising prognostic markers and effective therapeutic targets. In our previous study, we have found the elevated S100A6 in the ccRCC tumor tissues, and the differentially expressed genes determined by microarray analysis were found to be strongly related to tumor metastasis after S100A6 knockdown and overexpression in the ccRCC cell line 786-O. The mRNA expression of S100A6 detected by RT-PCR in 6 cell lines and 174 tumor tissues, including 58 metastatic ccRCC and 116 clinicopathological features paired non-metastatic ccRCC (1:2), indicated S100A6 was elevated in the metastatic cells and tumor tissues. The protein expression was consistent with mRNA expression. The biological function of S100A6 in promoting metastasis was determined through overexpression and knockdown of S100A6 in the ccRCC cell lines 786-O, caki-1, and ACHN. In the scratch wound migration assay as well as migration and invasion assays, S100A6 knockdown significantly suppressed the migratory and invasive abilities of tumor cells, whereas overexpression enhanced the malignancy. Further research with the follow-up data of 129 ccRCC patients were analyzed by the Cox regression and survival analysis. The expression of S100A6 was up-regulated in metastatic ccRCC cells. In the metastatic tumor tissues, the expression of S100A6 was also higher than in the non-metastatic tissues. High S100A6 expression might be crucial to promote metastasis in ccRCC by enhancing the ability of tumor cells migration and invasion. In addition, the quantitative mRNA expression of S100A6 in the tumor tissues was an independent risk factor and might be used as a prognostic marker for the metastatic risk of the localized T1–T2 stage ccRCC.

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Acknowledgments

This work was funded by National Natural Science Foundation of China (Nos. 81100483 and 30972982); and National High Technology Research and Development Program of China (863 Program) (No. 2012AA021100). We are grateful to Dr. Xiao-Ping Zhang of Wuhan Union Hospital for providing the SN12-PM6 cell lines. The authors also gratefully acknowledge Professors Ailing Li (Academy of Military Medical Sciences) and Tong Sun (Harvard Medical School) for providing valuable scientific discussions.

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All of the authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Urology, State Key Laboratory of Kidney Diseases, Chinese People’s Liberation Army General Hospital, Chinese PLA Medical School, Beijing, 100853, People’s Republic of China

    Xiangjun Lyu, Hongzhao Li, Xin Ma, Xintao Li, Yu Gao, Dong Ni, Donglai Shen, Liangyou Gu, Baojun Wang, Yu Zhang & Xu Zhang

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  1. Xiangjun Lyu
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  2. Hongzhao Li
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  3. Xin Ma
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Correspondence to Xu Zhang.

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Xiangjun Lyu and Hongzhao Li have contributed equally to this study.

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Lyu, X., Li, H., Ma, X. et al. High-Level S100A6 Promotes Metastasis and Predicts the Outcome of T1–T2 Stage in Clear Cell Renal Cell Carcinoma. Cell Biochem Biophys 71, 279–290 (2015). https://doi.org/10.1007/s12013-014-0196-x

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