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Published on: February 28, 2017

Calcium/calmodulin-dependent kinase II regulates notch-1 signaling in prostate cancer cells

Olga A Mamaeva1, Junghyun Kim, Gong Feng

  • 1Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35249-7331, USA.

Journal of Cellular Biochemistry
|November 21, 2008
PubMed

Insights

Calcium/calmodulin-dependent kinase II (CaMKII) interacts with Notch-1 signaling in prostate cancer bone metastasis. Inhibiting CaMKII or gamma-secretase impacts cancer cell proliferation and invasion, suggesting new therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Notch signaling is implicated in prostate cancer bone metastases.
  • Calcium/calmodulin-dependent kinase II (CaMKII) is crucial for osteoblastogenesis.
  • Prostate cancer cell lines exhibit differential Notch-1 receptor and CaMKII isoform expression based on metastatic origin.

Purpose of the Study:

  • To investigate the relationship between CaMKII and Notch-1 signaling in prostate cancer bone metastasis.
  • To explore the functional consequences of inhibiting CaMKII and Notch signaling on cancer cell behavior.

Main Methods:

  • Comparative analysis of Notch-1 and CaMKII expression in prostate cancer cell lines.
  • Pharmacological inhibition of CaMKII (KN93) and gamma-secretase (L-685,458).
  • siRNA-mediated knockdown and overexpression of CaMKII isoforms.
  • Assessment of downstream Notch signaling markers (Hes-1, c-Myc), cell proliferation, and invasion.

Main Results:

  • Prostate cancer cells from bone metastases (C4-2B, PC3) express Notch-1 and all CaMKII isoforms, unlike non-metastatic cells (LNcaP, DU145).
  • Inhibition of CaMKII or gamma-secretase reduced cleaved Notch-1, Hes-1 expression, and c-Myc levels.
  • Both inhibitors suppressed proliferation and Matrigel invasion of C4-2B cells.
  • CaMKII-alpha overexpression enhanced Hes-1 expression, indicating CaMKII's role in Notch-1 signaling.

Conclusions:

  • A novel crosstalk exists between CaMKII and Notch-1 pathways in prostate cancer bone metastasis.
  • CaMKII activity is essential for Notch-1 signaling, proliferation, and invasion in metastatic prostate cancer cells.
  • This interaction presents potential therapeutic targets for treating prostate cancer bone metastases.

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