SAM68: Signal Transduction and RNA Metabolism in Human Cancer

Abstract EN

Alterations in expression and/or activity of splicing factors as well as mutations in cis-actingsplicing regulatory sequences contribute to cancer phenotypes.

Genome-widestudies have revealed more than 15,000 tumor-associated splice variants derived fromgenes involved in almost every aspect of cancer cell biology, including proliferation,differentiation, cell cycle control, metabolism, apoptosis, motility, invasion, andangiogenesis.

In the past decades, several RNA binding proteins (RBPs) have beenimplicated in tumorigenesis.

SAM68 (SRC associated in mitosis of 68 kDa) belongs tothe STAR (signal transduction and activation of RNA metabolism) family of RBPs.

SAM68 is involved in several steps of mRNA metabolism, from transcription toalternative splicing and then to nuclear export.

Moreover, SAM68 participates in signalingpathways associated with cell response to stimuli, cell cycle transitions, and viralinfections.

Recent evidence has linked this RBP to the onset and progression ofdifferent tumors, highlighting misregulation of SAM68-regulated splicing events as akey step in neoplastic transformation and tumor progression.

Here we review recentstudies on the role of SAM68 in splicing regulation and we discuss its contribution toaberrant pre-mRNA processing in cancer.