Journal of Experimental & Clinical Cancer Research (Aug 2019)

Cripto-1 expression in patients with clear cell renal cell carcinoma is associated with poor disease outcome

  • Yi-Jun Xue,
  • Song-Ning Chen,
  • Wei-Guang Chen,
  • Geng-Qing Wu,
  • Yun-Feng Liao,
  • Jian-Bin Xu,
  • Hao Tang,
  • Shui-Hua Yang,
  • Shui-Yong He,
  • Yun-Fei Luo,
  • Zhi-Hui Wu,
  • Hai-Wen Huang

DOI
https://doi.org/10.1186/s13046-019-1386-6
Journal volume & issue
Vol. 38, no. 1
pp. 1 – 17

Abstract

Read online

Abstract Background Cripto-1 (CR-1) has been reported to be involved in the development of several human cancers. The potential role of CR-1 in clear cell renal cell carcinoma (ccRCC) is still not clear. Methods CR-1 expression was evaluated in ccRCC tissues by Real-time quantitative PCR, Western blot and immunohistochemistry. Serum levels of CR-1 were tested by enzyme-linked immunosorbent assay (ELISA). The clinical significance of CR-1 was analyzed. The effects of CR-1 on cell proliferation, migration, invasion and angiogenesis were investigated in ccRCC cell lines in vitro and in vivo, and markers of the epithelial -mesenchymal transition (EMT) were analyzed. The impact of CR-1 on Wnt/β-catenin signaling pathway was also evaluated in vitro and in vivo. Results CR-1 expression was elevated in ccRCC tumor tissues and serum samples. CR-1 expression was correlated with aggressive tumor phenotype and poor survival. Ectopic expression of CR-1 significantly promoted cell proliferation, migration, invasion and angiogenesis whereas knockdown of CR-1 inhibited these activities both in vitro and in vivo. Moreover, we found that CR-1 induced EMT and activated Wnt/β-catenin signaling pathway both in vitro and in vivo. Conclusions These results suggest that CR-1 is likely to play important roles in ccRCC development and progression, and that CR-1 is a prognostic biomarker and a promising therapeutic target for ccRCC.

Keywords