Authors:
 Lakshmi Kadkol, Shane Comiskey, Donald Vander Griend
 
 
 Affiliations:
 University of Illinois at Chicago
 
 
 Abstract Body:
 "There is currently no durable cure for prostate cancer (PCa) once it metastasizes. To discover new targets for more successful, patient-tailored therapeutic strategies for advanced PCa, it is critical to understand how the cancer progresses. While targetable kinase signaling cascades are intensely investigated in PCa, the phosphatases that regulate kinases and other proteins are vastly understudied, with the exception of PTEN, one of the most highly deregulated tumor suppressors in PCa.
 An inquiry of 255 phosphatases in the TCGA primary PCa database revealed that PPP2CB (PP2A catalytic subunit beta) is more frequently deregulated than PTEN, comprising ~30% of all cases. The majority display either decreased mRNA expression or deep deletion, also commonly observed in other patient datasets. These events do not significantly co-occur with PTEN and the gene resides on a different chromosome (8p12 versus 12q23), precluding a bystander effect of PTEN loss. PPP2CB loss is associated with poor survival and metastasis. Therefore, we hypothesize that PPP2CB loss can drive PCa aggressiveness and/or castration resistance.
 To study this, we have successfully developed and validated several new hormone-therapy sensitive and castration resistant (CRPC) cell models of PPP2CB loss via CRISPR gene knockout and are investigating the impact on proliferation and metastatic potential, as well as response to hormone deprivation and standard-of-care androgen receptor targeted therapies.
 Unraveling the underlying biology by which altered phosphatase signaling can promote cancer aggressiveness and progression will likely result in new putative biomarkers for predicting cancer outcomes, as well as the discovery of novel putative targets for therapeutic intervention toward eliminating death from prostate cancer."
 
 
 Funding Acknowledgments:
 PCF Young Investigator Award, AUA Research Scholar Award
 
 
 Corresponding Author Email:
 rdeleeuw@uic.edu
 
 
 Conflict of Interest:
 Nothing to Disclose

PPP2CB loss in prostate cancer progression