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p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma.

Publication ,  Journal Article
Li, Z; Sun, Y; Chen, X; Squires, J; Nowroozizadeh, B; Liang, C; Huang, J
Published in: Mol Cancer Res
March 2015

UNLABELLED: Prostatic small cell neuroendocrine carcinoma (SCNC) is a rare but aggressive form of prostate cancer that is negative for androgen receptor (AR) and not responsive to hormonal therapy. The molecular etiology of this prostate cancer variant is not well understood; however, mutation of the p53 (TP53) tumor suppressor in prostate neuroendocrine cells inactivates the IL8-CXCR2-p53 pathway that normally inhibits cellular proliferation, leading to the development of SCNC. SCNC also overexpresses Aurora kinase A (AURKA) which is considered to be a viable therapeutic target. Therefore, the relationship of these two molecular events was studied, and we show that p53 mutation leads to increased expression of miR-25 and downregulation of the E3 ubiquitin ligase FBXW7, resulting in elevated levels of Aurora kinase A. This study demonstrates an intracellular pathway by which p53 mutation leads to Aurora kinase A expression, which is critically important for the rapid proliferation and aggressive behavior of prostatic SCNC. IMPLICATIONS: The pathogenesis of prostatic SCNC involves a p53 and Aurora Kinase A signaling mechanism, both potentially targetable pathways.

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Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

March 2015

Volume

13

Issue

3

Start / End Page

584 / 591

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Protein p53
  • Signal Transduction
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Mutation
  • MicroRNAs
  • Male
  • Humans
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
Chicago
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MLA
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Li, Z., Sun, Y., Chen, X., Squires, J., Nowroozizadeh, B., Liang, C., & Huang, J. (2015). p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma. Mol Cancer Res, 13(3), 584–591. https://doi.org/10.1158/1541-7786.MCR-14-0277-T
Li, Zhen, Yin Sun, Xufeng Chen, Jill Squires, Behdokht Nowroozizadeh, Chaozhao Liang, and Jiaoti Huang. “p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma.Mol Cancer Res 13, no. 3 (March 2015): 584–91. https://doi.org/10.1158/1541-7786.MCR-14-0277-T.
Li Z, Sun Y, Chen X, Squires J, Nowroozizadeh B, Liang C, et al. p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma. Mol Cancer Res. 2015 Mar;13(3):584–91.
Li, Zhen, et al. “p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma.Mol Cancer Res, vol. 13, no. 3, Mar. 2015, pp. 584–91. Pubmed, doi:10.1158/1541-7786.MCR-14-0277-T.
Li Z, Sun Y, Chen X, Squires J, Nowroozizadeh B, Liang C, Huang J. p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma. Mol Cancer Res. 2015 Mar;13(3):584–591.

Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

March 2015

Volume

13

Issue

3

Start / End Page

584 / 591

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Suppressor Protein p53
  • Signal Transduction
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Mutation
  • MicroRNAs
  • Male
  • Humans
  • Gene Expression Regulation, Neoplastic