SAM68: Signal Transduction and RNA Metabolism in Human Cancer.
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.
Laboratory of Cellular and Molecular Neurobiology, Santa Lucia Foundation, 00143 Rome, Italy.
Paola
P
Frisone
Institute of Molecular Genetics-National Research Council (IGM-CNR), 27100 Pavia, Italy.
Davide
D
Pradella
Institute of Molecular Genetics-National Research Council (IGM-CNR), 27100 Pavia, Italy.
Anna
A
Di Matteo
Institute of Molecular Genetics-National Research Council (IGM-CNR), 27100 Pavia, Italy.
Elisa
E
Belloni
Institute of Molecular Genetics-National Research Council (IGM-CNR), 27100 Pavia, Italy.
Claudia
C
Ghigna
Laboratory of Cellular and Molecular Neurobiology, Santa Lucia Foundation, 00143 Rome, Italy ; University of Rome "Foro Italico", Piazza Lauro de Bosis 15, 00135 Rome, Italy.
Maria Paola
MP
Paronetto
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins