Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1
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Cysteine-rich secretory protein 3 (CRISP-3) is upregulated in prostate cancer as compared to the normal prostate tissue. Higher expression of CRISP-3 has been linked to poor prognosis and hence it has been thought to act as a prognostic marker for prostate cancer. It is proposed to have a role in innate immunity but its role in prostate cancer is still unknown. In order to understand its function, its expression was stably knocked down in LNCaP cells. CRISP-3 knockdown did not affect cell viability but resulted in reduced invasiveness. Global gene expression changes upon CRISP-3 knockdown were identified by microarray analysis. Microarray data were quantitatively validated by evaluating the expression of seven candidate genes in three independent stable clones. Functional annotation of the differentially expressed genes identified cell adhesion, cell motility, and ion transport to be affected among other biological processes. Prostate-specific antigen (PSA, also known as Kallikrein 3) was the top most downregulated gene whose expression was also validated at protein level. Interestingly, expression of Annexin A1 (ANXA1), a known anti-inflammatory protein, was upregulated upon CRISP-3 knockdown. Re-introduction of CRISP-3 into the knockdown clone reversed the effect on invasiveness and also led to increased PSA expression. These results suggest that overexpression of CRISP-3 in prostate tumor may maintain higher PSA expression and lower ANXA1 expression. Our data also indicate that poor prognosis associated with higher CRISP-3 expression could be due to its role in cell invasion.
KeywordsCRISP-3 Prostate cancer Prognosis shRNA PSA ANXA1
The research work related to this publication (RA/210/12-2014) was supported by grants from the Indian Council of Medical Research and DAE-BRNS, India (2011/37B/40/BRNS). Technical assistance provided by Ms. Anita Pote is acknowledged. We acknowledge Dr. Srabani Mukherjee and Ms. Nanda Joshi for their help with DNA sequencing. We are thankful to Dr. Nafisa Balasinor, Ms. Reshma Gaonkar and Ms. Shobha Sonawane for their help with confocal microscope.
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Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Grupp K, Kohl S, Sirma H, Simon R, Steurer S, Becker A et al (2013) Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence. Mod Pathol 26:733–742. doi: 10.1038/modpathol.2012.206 CrossRefPubMedGoogle Scholar
- 10.Niderman T, Genetet I, Bruyère T, Gees R, Stintzi A, Legrand M et al (1995) Pathogenesis-related PR-1 proteins are antifungal. Isolation and characterization of three 14-kilodalton proteins of tomato and of a basic PR-1 of tobacco with inhibitory activity against Phytophthora infestans. Plant Physiol 108:17–27PubMedCentralCrossRefPubMedGoogle Scholar