The Potential Tumor-Suppressor DHRS7 Inversely Correlates with EGFR Expression in Prostate Cancer Cells and Tumor

Simon Stücheli1, Selene Araya1, Caner Ercan2,3

  • 1Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.

Cancers
|July 9, 2022
PubMed

Insights

Dehydrogenase/reductase 7 (DHRS7) may protect against prostate cancer (PCa) progression. Lower DHRS7 levels correlate with increased epidermal growth factor receptor (EGFR) and poorer outcomes in PCa patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate cancer (PCa) is a leading cause of cancer death in men, often developing therapy resistance and metastasis.
  • Dehydrogenase/reductase 7 (DHRS7) is an orphan enzyme with an unknown physiological role, previously found to be downregulated in advanced PCa.
  • DHRS7 knockdown in LNCaP cells increased cancer cell aggressiveness, suggesting a potential tumor-suppressive function.

Purpose of the Study:

  • To investigate the role of DHRS7 in prostate cancer (PCa) pathogenesis.
  • To identify molecular pathways altered by DHRS7 expression changes in PCa cells.
  • To explore the relationship between DHRS7, androgen receptor (AR) signaling, and epidermal growth factor receptor (EGFR) in PCa.

Main Methods:

  • Proteomic analysis of LNCaP cells following DHRS7 knockdown.
  • Validation of protein expression changes using RT-qPCR and Western blotting.
  • Correlation analysis of DHRS7 and EGFR expression in different PCa cell lines and patient samples.

Main Results:

  • DHRS7 knockdown led to increased expression of epidermal growth factor receptor (EGFR) in PCa cells, independent of AR signaling.
  • A negative correlation was observed between DHRS7 and EGFR expression across various PCa cell lines (LNCaP, PC-3, DU145).
  • Analysis of patient samples confirmed a negative correlation between DHRS7 and EGFR expression at both mRNA and protein levels.
  • Higher DHRS7 expression in patients correlated positively with improved survival rates.

Conclusions:

  • DHRS7 may play a protective role in prostate cancer, potentially by downregulating EGFR.
  • The DHRS7-EGFR axis represents a potential therapeutic target for managing PCa progression.
  • DHRS7's function in PCa appears to be independent of the androgen receptor pathway.

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