Splicing Factor Kinase SRPK1 Regulates Metastatic Dissemination of Human Prostate Cancer
Abstract
Cancer cells spread throughout the body to distal sites in process known as metastasis. Metastatic disease is the cause of the vast majority of cancer-associated deaths. However, to date there are no anti-cancer drugs that specifically target the spread of cancer cells. Furthermore, there are no molecular markers that can accurately predict the risks of metastatic disease in the vast majority of cancers, including prostate cancer. Prostate cancer is the number one diagnosed cancer in American men. In 2014, there will be approximately 233,000 newly diagnosed cases of prostate cancer resulting in 29,480 premature deaths nationally. Furthermore, recent research shows that military personnel suffer a disproportionally higher rate of prostate cancer than the general public, thereby making this disease a substantial financial burden on the Department of Defense. Despite its significant impact on men s health, there are no clinically available drugs that specifically prevent prostate cancer metastasis. Furthermore, measurement of prostate serum antigen (PSA) levels has been used as a marker for prostate cancer; however, recent findings that PSA is a poor prognosticator of clinical outcome left clinical oncologists without a diagnostic blood test for this incredibly costly disease. Fortunately, the vast majority of prostate cancer outcomes are good even without treatment; however, in a number of patients the primary cancer will disseminate to distal sites throughout the body leading to advanced metastatic disease. All prostate cancer deaths are caused by metastasis. This highlights the need to develop prognostic tests that can predict a patient s risk of developing metastatic disease, and a requirement for novel therapeutic drugs that target metastatic progression. Our goal is to better understand how metastasis is regulated at the molecular level. In an unprecedented screen for regulators of cancer cell metastasis, we found many new molecular regulators that control the spread of cancer. In follow-up studies, we found that removing these critical regulators from cancer cells reduces the cancer s ability to spread. These critical regulators of metastasis may be strong clinical markers that might be used to identify malignant cancers or predict the likelihood of developing metastatic disease. Furthermore, these metastatic regulators represent exciting new drug targets to block the spread of cancer. Specifically, we identified the splicing factor kinase SRPK1 as a new regulator of prostate cancer cell metastasis. SRPK1 activity promotes cancer cell invasion and migration two critical steps in metastasis. Our preliminary data suggest that SRPK1 levels are elevated in advanced prostate cancer and metastatic tumors. Furthermore, SRPK1 is required for the generation of numerous pro-metastatic factors. We therefore believe that SRPK represents and ideal biomarker for the detection and diagnosis of advanced metastatic disease. Additionally, SRPK1 activity represents a novel therapeutic target for anti-metastatic drug development.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510327
Entities
People
- David Bond
Organizations
- United States Army
- University of Alberta