Expression of the beta 4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells.
The alpha 6 beta 4 integrin is the receptor for various laminin isoforms and is a component of the hemidesmosome. Increased expression levels of this integrin correlate with the aggressive phenotype of many epithelial tumors compared with surrounding normal tissue. Furthermore, the long cytoplasmic tail of the beta 4 integrin subunit has been implicated in several signal transduction pathways that are involved not only in invasion, but also in proliferation and apoptosis. Here we report that the exogenous expression of beta 4 integrin in 32D/v-abl-transformed cells reduces tumor aggressiveness in vivo and strongly inhibits cell proliferation in vitro by inducing monocytic differentiation. These effects are accompanied by growth arrest and p73 protein accumulation. The hypothesis that the inhibition of v-Abl oncogenic capacity could allow the activation of the endogenous c-Abl was tested in RKO cells. The results clearly demonstrated a strong increase of c-Abl phosphorylation that is accompanied by its association with p73 protein. Overall, the reported findings indicate that alpha 6 beta 4 integrin promotes growth arrest and differentiation by modulating Abl kinases and p73 protein pathway(s).
Morena
Annarita
A
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro, Rome, Italy.
Riccioni
Sabrina
S
Marchetti
Alessandra
A
Polcini
Alessandro Tartaglia
AT
Mercurio
Arthur M
AM
Blandino
Giovanni
G
Sacchi
Ada
A
Falcioni
Rita
R
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016147:Genes, Tumor Suppressor; D039161:Integrin alpha6beta4; D016023:Integrins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016374:Oncogene Proteins v-abl / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits; D015398:Signal Transduction / Q000187:drug effects; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D000954:Antigens, Surface; D004268:DNA-Binding Proteins; D039161:Integrin alpha6beta4; D016023:Integrins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016374:Oncogene Proteins v-abl; D021122:Protein Subunits; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D020928:Mitogen-Activated Protein Kinases