Molecular and biological consequences of targeting polyamine metabolism in prostate cancer

Abstract

The study of tumor metabolism has uncovered a new therapeutic window for the treatment of some cancer types. In such paradigm, cell signaling and metabolic reprogramming can act in tandem for the benefit of the cancer cell. Prostate cancer (PCa), the second most common cancer diagnosed in men worldwide, is a clear example of this convergence. Previous studies conducted in our lab have shown how polyamine (PA) biosynthesis is elevated in PCa with profound implications in the progression of the disease. However, PA deprivation therapy has failed in patients in the last years and currently, in spite of the conclusive data about the contribution of PAs to cancer biology, their molecular effectors remain obscure. In this thesis, we describe a mechanism orchestrated by activating transcription factor 4 (ATF4) signaling through which PCa cells could acquire survival properties and resistance to therapies targeting polyamine metabolism. In addition, we provide solid evidence about the regulatory function of PAs in the process of mRNA splicing through changes occurring at posttranslational level. Overall, our results expand the current knowledge about the role of PAs in both physiology and disease.