Open Access

SHISA2 enhances the aggressive phenotype in prostate cancer through the regulation of WNT5A expression

  • Authors:
    • Kenji Tamura
    • Mutsuo Furihata
    • Hirofumi Satake
    • Hatsune Hashida
    • Chiaki Kawada
    • Hiroto Osakabe
    • Hideo Fukuhara
    • Naoko Kumagai
    • Tatsuo Iiyama
    • Taro Shuin
    • Keiji Inoue
  • View Affiliations

  • Published online on: September 28, 2017     https://doi.org/10.3892/ol.2017.7099
  • Pages:6650-6658
  • Copyright: © Tamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed at identifying novel molecular cancer drug targets and biomarkers by analyzing the gene expression profiles of high‑grade prostate cancer (PC), using a cDNA microarray combined with laser microbeam microdissection. A number of genes were identified that were transactivated in high‑grade PC. First, a novel molecular target and diagnostic biomarker, shisa family member 2 (SHISA2), was identified as an overexpressed gene in high‑grade PC cells. The reverse transcription‑semi‑quantitative polymerase chain reaction and immunohistochemical analysis validated the overexpression of SHISA2 (295 amino acids in length), specifically in high‑grade PC cells with Gleason scores of between 8 and 10, relative to normal prostate epithelium. Knockdown of SHISA2 expression by short interfering RNA resulted in the marked suppression of PC cell viability. By contrast, exogenous SHISA2 expression in transfected cells promoted PC cell proliferation, indicating its oncogenic effects. Notably, as a result of cDNA microarray analysis, protein Wnt‑5a (WNT5A) was focused upon and the expression of WNT5A was identified to be downregulated in SHISA2‑knockdown. Western blot analysis validated significant downregulation of WNT5A by SHISA2‑knockdown and upregulation of WNT5A by SHISA2 overexpression. The results of the present study indicated that SHISA2 may affect WNT5A synthesis. Furthermore, the secreted SHISA2 protein was determined in the culture medium of PC cells. We hypothesize that SHISA2 is involved in the regulation of WNT5A and in the aggressiveness of PC via the Wnt signaling pathway through WNT5A. Furthermore, SHISA2 may be a molecular target for cancer drugs, and a useful diagnostic biomarker for the prognosis and therapeutic effect in cancer.

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December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Tamura, K., Furihata, M., Satake, H., Hashida, H., Kawada, C., Osakabe, H. ... Inoue, K. (2017). SHISA2 enhances the aggressive phenotype in prostate cancer through the regulation of WNT5A expression. Oncology Letters, 14, 6650-6658. https://doi.org/10.3892/ol.2017.7099
MLA
Tamura, K., Furihata, M., Satake, H., Hashida, H., Kawada, C., Osakabe, H., Fukuhara, H., Kumagai, N., Iiyama, T., Shuin, T., Inoue, K."SHISA2 enhances the aggressive phenotype in prostate cancer through the regulation of WNT5A expression". Oncology Letters 14.6 (2017): 6650-6658.
Chicago
Tamura, K., Furihata, M., Satake, H., Hashida, H., Kawada, C., Osakabe, H., Fukuhara, H., Kumagai, N., Iiyama, T., Shuin, T., Inoue, K."SHISA2 enhances the aggressive phenotype in prostate cancer through the regulation of WNT5A expression". Oncology Letters 14, no. 6 (2017): 6650-6658. https://doi.org/10.3892/ol.2017.7099