Signal transduction pathways of mantle cell lymphoma: a phosphoproteome-based study.
Mantle cell lymphoma (MCL) is an incurable hematologic malignancy whose pathogenesis is only partly understood. The aim of the present study was to define a "core phosphoproteome" in MCL cell lines that is representative of primary MCL in order to improve knowledge of the signal transduction pathways involved in its tumorigenesis. We have analyzed phosphorylated proteins in several MCL cell lines by immobilized metal affinity chromatography and separation by 2-D PAGE, followed by RP-HPLC coupled with MS/MS identification. These data were correlated with information on copy number gains obtained by SNP-chip analysis. Several of the proteins identified could be linked to a specific signal transduction pathway, and have been recently recognized as important players in MCL pathogenesis, such as nuclear factor-kappaB (NF-kappaB) and phosphoinositide-3 kinase-mammalian target of rapamycin (PI3K-mTOR). However, our data also implicate a number of novel proteins and pathways in the pathobiology of MCL, one of which is mitochondrial signaling. A second-level analysis identified MAPK1, CK2, CK1, PKCzeta, and PKCepsilon as candidate upstream molecules. Our study provides new insights in MCL pathogenesis and helps to form the basis for testing new target-specific therapeutics.
Cecconi
Daniela
D
Laboratorio di Proteomica, Dipartimento Scientifico e Tecnologico, University of Verona, Verona, Italy.
Zamò
Alberto
A
Bianchi
Elena
E
Parisi
Alice
A
Barbi
Stefano
S
Milli
Alberto
A
Rinalducci
Sara
S
Rosenwald
Andreas
A
Hartmann
Elena
E
Zolla
Lello
L
Chilosi
Marco
M
D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D018628:Gene Dosage; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D010750:Phosphoproteins; D020543:Proteome