Polyamines are small organic molecules required for multiple cellular functions including proliferation, growth, control of chromatin structure and transcription. Cancer cells require an abundance of polyamines through biosynthesis and transport to maintain their proliferative phenotype. An FDA approved drug (DFMO) that targets synthesis is often ineffective because malignant cells circumvent the therapy by up-regulating transport. Thus a combination therapy targeting both synthesis and transport simultaneously is highly desirable. Though synthesis is thoroughly explained, import through a polyamine transport system (PTS) remains undefined. Since polyamine transport is observed in all organisms this represents a major gap in our knowledge of a basic cellular process and hinders the development of effective drugs targeting the PTS.
Utilizing a team of undergraduate students supervised by graduate students, our lab conducted an RNAi-based genetic screen to identify components of the polyamine transport system. Starting with a previously identified gene encoding a family of P-type 5B ATPases we identified 29 genes with similar spatial and temporal expression profiles. These genes were then tested in a novel RNAi-based survival assay developed in our laboratory. As a result of the screen we identify RabX6, which is involved in endosomal transport as a novel component of the PTS.