Targeting CREB-Heparan Sulfate Pathway for Cancer Treatment

Advantages:

This research contributes to a better understanding of the molecular mechanisms underlying the development and progression of PCa.
The study identifies a specific signaling pathway involving Pten loss, CREB, and HS that plays a crucial role in promoting prostate tumorigenesis.
The study explores potential therapeutic interventions, such as knockdown of Ext1 or pharmacological inhibition of HS, which successfully block PCa growth in animal models.

Summary:

Prostate cancer (PCa) is one of the most prevalent forms of malignancy and the second most common cause of cancer related death in men. A better understanding of PCa pathogenesis is essential to improve our effort to cure this life-threatening disease. Heparan sulfate (HS), a linear, sulfated polysaccharide, expresses in the prostate and its expression is upregulated in PCa. Currently, what factors drive the aberrant HS expression and its functional consequence in PCa pathogenesis remain unclear.

Systematic bioinformatics studies at USF uncovered the loss-of-function mutation of Pten, a potent humor suppressor, correlates with upregulated heparan sulfate expression in human prostate cancer specimens. In mouse model and cell culture studies, the researchers uncovered that Pten-loss upregulates CREB-heparan sulfate signaling to promote prostate tumorigenesis, and pharmacological inhibition of CREB or heparan sulfate both efficiently blocked prostate cancer growth in vitro and in vivo, revealing the CREB-heparan sulfate axis as a novel target for cancer treatment.