The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Barbara Belletti - One of the best experts on this subject based on the ideXlab platform.
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stathmin activity influences Sarcoma Cell shape motility and metastatic potential
Molecular Biology of the Cell, 2008Co-Authors: Barbara Belletti, Stefania Berton, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Sara Dandrea, Francesca Lovat, Katarina Wolf, Antonella ZucchettoAbstract:The balanced activity of microtubule-stabilizing and -destabilizing proteins determines the extent of microtubule dynamics, which is implicated in many Cellular processes, including adhesion, migration, and morphology. Among the destabilizing proteins, stathmin is overexpressed in different human malignancies and has been recently linked to the regulation of Cell motility. The observation that stathmin was overexpressed in human recurrent and metastatic Sarcomas prompted us to investigate stathmin contribution to tumor local invasiveness and distant dissemination. We found that stathmin stimulated Cell motility in and through the extraCellular matrix (ECM) in vitro and increased the metastatic potential of Sarcoma Cells in vivo. On contact with the ECM, stathmin was negatively regulated by phosphorylation. Accordingly, a less phosphorylable stathmin point mutant impaired ECM-induced microtubule stabilization and conferred a higher invasive potential, inducing a rounded Cell shape coupled with amoeboid-like motility in three-dimensional matrices. Our results indicate that stathmin plays a significant role in tumor metastasis formation, a finding that could lead to exploitation of stathmin as a target of new antimetastatic drugs.
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p27kip1 stathmin interaction influences Sarcoma Cell migration and invasion
Cancer Cell, 2005Co-Authors: Gustavo Baldassarre, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Barbara Belletti, Andrea Vecchione, Paola Spessotto, Andrea Morrione, Alfonso ColombattiAbstract:Abstract Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate Cellular functions other than Cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27 kip1 affects microtubule (MT) stability following Cell adhesion on extraCellular matrix (ECM) constituents. This p27 kip1 activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27 kip1 or downregulation of stathmin expression results in the inhibition of mesenchymal Cell motility. Moreover, high stathmin and low cytoplasmic p27 kip1 expression correlate with the metastatic phenotype of human Sarcomas in vivo. This study provides a functional link between proliferation and invasion of tumor Cells based on diverse activities of p27 kip1 in different subCellular compartments.
Piergiorgio Modena - One of the best experts on this subject based on the ideXlab platform.
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smarcb1 ini1 genetic inactivation is responsible for tumorigenic properties of epithelioid Sarcoma Cell line vaesbj
Molecular Cancer Therapeutics, 2013Co-Authors: Monica Brenca, Sabrina Rossi, Erica Lorenzetto, Elena Piccinin, Sara Piccinin, Francesca Rossi, Alberto Giuliano, Angelo Paolo Dei Tos, Roberta Maestro, Piergiorgio ModenaAbstract:Epithelioid Sarcoma is a rare soft tissue neoplasm that usually arises in the distal extremities of young adults. Epithelioid Sarcoma presents a high rate of recurrences and metastases and frequently poses diagnostic dilemmas. We previously reported loss of tumor suppressor SMARCB1 protein expression and SMARCB1 gene deletion in the majority of epithelioid Sarcoma cases. Unfortunately, no appropriate preclinical models of such genetic alteration in epithelioid Sarcoma are available. In the present report, we identified lack of SMARCB1 protein due to a homozygous deletion of exon 1 and upstream regulatory region in epithelioid Sarcoma Cell line VAESBJ. Restoration of SMARCB1 expression significantly affected VAESBJ Cell proliferation, anchorage-independent growth, and Cell migration properties, thus supporting the causative role of SMARCB1 loss in epithelioid Sarcoma pathogenesis. We investigated the translational relevance of this genetic background in epithelioid Sarcoma and showed that SMARCB1 ectopic expression significantly augmented VAESBJ sensitivity to gamma irradiation and acted synergistically with flavopiridol treatment. In VAESBJ, both activated ERBB1/EGFR and HGFR/MET impinged on AKT and ERK phosphorylation. We showed a synergistic effect of combined inhibition of these 2 receptor tyrosine kinases using selective small-molecule inhibitors on Cell proliferation. These observations provide definitive support to the role of SMARCB1 inactivation in the pathogenesis of epithelioid Sarcoma and disclose novel clues to therapeutic approaches tailored to SMARCB1-negative epithelioid Sarcoma.
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smarcb1 ini1 genetic inactivation is responsible for tumorigenic properties of epithelioid Sarcoma Cell line vaesbj
Molecular Cancer Therapeutics, 2013Co-Authors: Monica Brenca, Sabrina Rossi, Erica Lorenzetto, Elena Piccinin, Sara Piccinin, Alberto Giuliano, Roberta Maestro, Francesca Maria Rossi, Piergiorgio ModenaAbstract:Epithelioid Sarcoma (ES) is a rare soft tissue neoplasm that usually arises in the distal extremities of young adults. ES presents a high rate of recurrences and metastases and frequently poses diagnostic dilemmas. We previously reported loss of tumor suppressor SMARCB1 protein expression and SMARCB1 gene deletion in the majority of ES cases. Unfortunately, no appropriate pre-clinical models of such genetic alteration in ES are available. In the present report we identified lack of SMARCB1 protein due to a homozygous deletion of exon 1 and upstream regulatory region in epithelioid Sarcoma Cell line VAESBJ. Restoration of SMARCB1 expression significantly affected VAESBJ Cell proliferation, anchorage-independent growth and Cell migration properties, thus supporting the causative role of SMARCB1 loss in ES pathogenesis. We investigated the translational relevance of this genetic background in ES and demonstrated that SMARCB1 ectopic expression significantly augmented VAESBJ sensitivity to gamma irradiation and acted synergistically with Flavopiridol treatment. In VAESBJ, both activated ERBB1/EGFR and HGFR/MET impinged on AKT and ERK phosphorylation. We demonstrated a synergistic effect of combined inhibition of these two receptor tyrosine kinases using selective small molecule inhibitors on Cell proliferation. These observations provide definitive support to the role of SMARCB1 inactivation in the pathogenesis of epithelioid Sarcoma and disclose novel clues to therapeutic approaches tailored to SMARCB1-negative ES.
Monica Schiappacassi - One of the best experts on this subject based on the ideXlab platform.
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stathmin activity influences Sarcoma Cell shape motility and metastatic potential
Molecular Biology of the Cell, 2008Co-Authors: Barbara Belletti, Stefania Berton, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Sara Dandrea, Francesca Lovat, Katarina Wolf, Antonella ZucchettoAbstract:The balanced activity of microtubule-stabilizing and -destabilizing proteins determines the extent of microtubule dynamics, which is implicated in many Cellular processes, including adhesion, migration, and morphology. Among the destabilizing proteins, stathmin is overexpressed in different human malignancies and has been recently linked to the regulation of Cell motility. The observation that stathmin was overexpressed in human recurrent and metastatic Sarcomas prompted us to investigate stathmin contribution to tumor local invasiveness and distant dissemination. We found that stathmin stimulated Cell motility in and through the extraCellular matrix (ECM) in vitro and increased the metastatic potential of Sarcoma Cells in vivo. On contact with the ECM, stathmin was negatively regulated by phosphorylation. Accordingly, a less phosphorylable stathmin point mutant impaired ECM-induced microtubule stabilization and conferred a higher invasive potential, inducing a rounded Cell shape coupled with amoeboid-like motility in three-dimensional matrices. Our results indicate that stathmin plays a significant role in tumor metastasis formation, a finding that could lead to exploitation of stathmin as a target of new antimetastatic drugs.
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p27kip1 stathmin interaction influences Sarcoma Cell migration and invasion
Cancer Cell, 2005Co-Authors: Gustavo Baldassarre, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Barbara Belletti, Andrea Vecchione, Paola Spessotto, Andrea Morrione, Alfonso ColombattiAbstract:Abstract Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate Cellular functions other than Cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27 kip1 affects microtubule (MT) stability following Cell adhesion on extraCellular matrix (ECM) constituents. This p27 kip1 activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27 kip1 or downregulation of stathmin expression results in the inhibition of mesenchymal Cell motility. Moreover, high stathmin and low cytoplasmic p27 kip1 expression correlate with the metastatic phenotype of human Sarcomas in vivo. This study provides a functional link between proliferation and invasion of tumor Cells based on diverse activities of p27 kip1 in different subCellular compartments.
Vincenzo Canzonieri - One of the best experts on this subject based on the ideXlab platform.
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stathmin activity influences Sarcoma Cell shape motility and metastatic potential
Molecular Biology of the Cell, 2008Co-Authors: Barbara Belletti, Stefania Berton, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Sara Dandrea, Francesca Lovat, Katarina Wolf, Antonella ZucchettoAbstract:The balanced activity of microtubule-stabilizing and -destabilizing proteins determines the extent of microtubule dynamics, which is implicated in many Cellular processes, including adhesion, migration, and morphology. Among the destabilizing proteins, stathmin is overexpressed in different human malignancies and has been recently linked to the regulation of Cell motility. The observation that stathmin was overexpressed in human recurrent and metastatic Sarcomas prompted us to investigate stathmin contribution to tumor local invasiveness and distant dissemination. We found that stathmin stimulated Cell motility in and through the extraCellular matrix (ECM) in vitro and increased the metastatic potential of Sarcoma Cells in vivo. On contact with the ECM, stathmin was negatively regulated by phosphorylation. Accordingly, a less phosphorylable stathmin point mutant impaired ECM-induced microtubule stabilization and conferred a higher invasive potential, inducing a rounded Cell shape coupled with amoeboid-like motility in three-dimensional matrices. Our results indicate that stathmin plays a significant role in tumor metastasis formation, a finding that could lead to exploitation of stathmin as a target of new antimetastatic drugs.
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p27kip1 stathmin interaction influences Sarcoma Cell migration and invasion
Cancer Cell, 2005Co-Authors: Gustavo Baldassarre, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Barbara Belletti, Andrea Vecchione, Paola Spessotto, Andrea Morrione, Alfonso ColombattiAbstract:Abstract Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate Cellular functions other than Cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27 kip1 affects microtubule (MT) stability following Cell adhesion on extraCellular matrix (ECM) constituents. This p27 kip1 activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27 kip1 or downregulation of stathmin expression results in the inhibition of mesenchymal Cell motility. Moreover, high stathmin and low cytoplasmic p27 kip1 expression correlate with the metastatic phenotype of human Sarcomas in vivo. This study provides a functional link between proliferation and invasion of tumor Cells based on diverse activities of p27 kip1 in different subCellular compartments.
Milena S Nicoloso - One of the best experts on this subject based on the ideXlab platform.
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stathmin activity influences Sarcoma Cell shape motility and metastatic potential
Molecular Biology of the Cell, 2008Co-Authors: Barbara Belletti, Stefania Berton, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Sara Dandrea, Francesca Lovat, Katarina Wolf, Antonella ZucchettoAbstract:The balanced activity of microtubule-stabilizing and -destabilizing proteins determines the extent of microtubule dynamics, which is implicated in many Cellular processes, including adhesion, migration, and morphology. Among the destabilizing proteins, stathmin is overexpressed in different human malignancies and has been recently linked to the regulation of Cell motility. The observation that stathmin was overexpressed in human recurrent and metastatic Sarcomas prompted us to investigate stathmin contribution to tumor local invasiveness and distant dissemination. We found that stathmin stimulated Cell motility in and through the extraCellular matrix (ECM) in vitro and increased the metastatic potential of Sarcoma Cells in vivo. On contact with the ECM, stathmin was negatively regulated by phosphorylation. Accordingly, a less phosphorylable stathmin point mutant impaired ECM-induced microtubule stabilization and conferred a higher invasive potential, inducing a rounded Cell shape coupled with amoeboid-like motility in three-dimensional matrices. Our results indicate that stathmin plays a significant role in tumor metastasis formation, a finding that could lead to exploitation of stathmin as a target of new antimetastatic drugs.
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p27kip1 stathmin interaction influences Sarcoma Cell migration and invasion
Cancer Cell, 2005Co-Authors: Gustavo Baldassarre, Milena S Nicoloso, Monica Schiappacassi, Vincenzo Canzonieri, Barbara Belletti, Andrea Vecchione, Paola Spessotto, Andrea Morrione, Alfonso ColombattiAbstract:Abstract Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate Cellular functions other than Cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27 kip1 affects microtubule (MT) stability following Cell adhesion on extraCellular matrix (ECM) constituents. This p27 kip1 activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27 kip1 or downregulation of stathmin expression results in the inhibition of mesenchymal Cell motility. Moreover, high stathmin and low cytoplasmic p27 kip1 expression correlate with the metastatic phenotype of human Sarcomas in vivo. This study provides a functional link between proliferation and invasion of tumor Cells based on diverse activities of p27 kip1 in different subCellular compartments.
