Journal
ONCOTARGET
Volume 8, Issue 58, Pages 98298-98311Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.21176
Keywords
prostate cancer; cancer progression; apoptosis; metabolism; Ca2+ signalling
Categories
Funding
- Cancerfonden
- Swedish Research Council [2016-01142, 15 0736]
- Swedish Government Funds for Clinical research
- Foundation of Gunnar Nilsson
- Foundation of Malmo Cancer
- Foundation of Osterlund
- Foundation of King Gustav V's 80th anniversary
- Foundation of Knut and Alice Wallenberg
- Foundation of Inga-Britt and Arne Lundberg
- Vinnova [2016-01142] Funding Source: Vinnova
- Swedish Research Council [2016-01142] Funding Source: Swedish Research Council
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Cartilage oligomeric matrix protein (COMP) was recently implicated in the progression of breast cancer. Immunostaining of 342 prostate cancer specimens in tissue microarrays showed that COMP expression is not breast cancer-specific but also occurs in prostate cancer. The expression of COMP in prostate cancer cells correlated with a more aggressive disease with faster recurrence. Subcutaneous xenografts in immunodeficient mice showed that the prostate cancer cell line DU145 overexpressing COMP formed larger tumors in vivo as compared to mock-transfected cells. Purified COMP bound to and enhanced the invasion of DU145 cells in vitro in an integrin-dependent manner. In addition, intracellular COMP expression interfered with cellular metabolism by causing a decreased level of oxidative phosphorylation with a concurrent upregulation of lactate production (Warburg effect). Further, expression of COMP protected cells from induction of apoptosis via several pathways. The effect of COMP on metabolism and apoptosis induction was dependent on the ability of COMP to disrupt intracellular Ca2+ signalling by preventing Ca2+ release from the endoplasmic reticulum. In conclusion, COMP is a potent driver of the progression of prostate cancer, acting in an anti-apoptotic fashion by interfering with the Ca2+ homeostasis of cancer cells.
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