Alterations in expression and/or activity of
splicing factors as well as mutations in cis-acting splicing regulatory sequences contribute to
cancer phenotypes. Genome-wide studies have revealed more than 15,000
tumor-associated splice variants derived from genes involved in almost every aspect of
cancer cell biology, including proliferation, differentiation, cell cycle control, metabolism, apoptosis, motility, invasion, and angiogenesis. In the past decades, several
RNA binding proteins (RBPs) have been implicated in
tumorigenesis. SAM68 (SRC associated in mitosis of 68 kDa) belongs to the STAR (signal transduction and activation of
RNA metabolism) family of RBPs. SAM68 is involved in several steps of
mRNA metabolism, from transcription to alternative splicing and then to nuclear export. Moreover, SAM68 participates in signaling pathways associated with cell response to stimuli, cell cycle transitions, and
viral infections. Recent evidence has linked this RBP to the onset and progression of different
tumors, highlighting misregulation of SAM68-regulated splicing events as a key step in neoplastic transformation and
tumor progression. Here we review recent studies on the role of SAM68 in splicing regulation and we discuss its contribution to aberrant
pre-mRNA processing in
cancer.