title: High-level S100A6 promotes metastasis and predicts the outcome of T1-T2 stage in clear cell renal cell carcinoma.
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.
authors.affiliation: 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.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Lyu
authors.forename: Hongzhao
authors.initials: H
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Xintao
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Dong
authors.initials: D
authors.lastname: Ni
authors.forename: Donglai
authors.initials: D
authors.lastname: Shen
authors.forename: Liangyou
authors.initials: L
authors.lastname: Gu
authors.forename: Baojun
authors.initials: B
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012306:Risk; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human