Dual-specificity phosphatase 6 (DUSP6, mitogen-activated protein kinase (MAPK) phosphatase 3 or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on extracellular signal-regulated kinase (ERK1/2; MAPK1/2) to inactivate the ERK1/2 kinase. DUSP6 is a critical regulator of the ERK signaling cascade and has been implicated as a tumor suppressor. We report here experimental evidences that DUSP6 is transcriptionally upregulated in primary and long-term cultures of human glioblastoma, as assayed by northern hybridization and real-time quantitative PCR, producing constitutive high level of protein expression. Functional assays were performed with adenovirus-mediated expression of DUSP6 in glioblastoma cultures. Protein overexpression inhibits growth by inducing G1-phase delay and increased mitogenic/anchorage dependence and clonogenic potential in vitro. Changes in cell morphology were associated with an increased tumor growth in vivo. Chemoresistance is a major cause of treatment failure and poor outcome in human glioblastomas. Importantly, DUSP6 overexpression increased resistance to cisplatin-mediated cell death in vitro and in vivo. Antisense-mediated depletion of DUSP6 acted in lowering the threshold to anticancer DNA-damaging drugs. We conclude that upregulation of DUSP6 exerts a tumor-promoting role in human glioblastomas exacerbating the malignant phenotype. Oncogene (2011) 30, 3813-3820; doi:10.1038/onc.2011.99; published online 18 April 2011

Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas / S., Messina; Frati, Luigi; C., Leonetti; C., Zuchegna; E., Di Zazzo; Calogero, Antonella; A., Porcellini. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 30:35(2011), pp. 3813-3820. [10.1038/onc.2011.99]

Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas

FRATI, Luigi;CALOGERO, ANTONELLA;
2011

Abstract

Dual-specificity phosphatase 6 (DUSP6, mitogen-activated protein kinase (MAPK) phosphatase 3 or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on extracellular signal-regulated kinase (ERK1/2; MAPK1/2) to inactivate the ERK1/2 kinase. DUSP6 is a critical regulator of the ERK signaling cascade and has been implicated as a tumor suppressor. We report here experimental evidences that DUSP6 is transcriptionally upregulated in primary and long-term cultures of human glioblastoma, as assayed by northern hybridization and real-time quantitative PCR, producing constitutive high level of protein expression. Functional assays were performed with adenovirus-mediated expression of DUSP6 in glioblastoma cultures. Protein overexpression inhibits growth by inducing G1-phase delay and increased mitogenic/anchorage dependence and clonogenic potential in vitro. Changes in cell morphology were associated with an increased tumor growth in vivo. Chemoresistance is a major cause of treatment failure and poor outcome in human glioblastomas. Importantly, DUSP6 overexpression increased resistance to cisplatin-mediated cell death in vitro and in vivo. Antisense-mediated depletion of DUSP6 acted in lowering the threshold to anticancer DNA-damaging drugs. We conclude that upregulation of DUSP6 exerts a tumor-promoting role in human glioblastomas exacerbating the malignant phenotype. Oncogene (2011) 30, 3813-3820; doi:10.1038/onc.2011.99; published online 18 April 2011
2011
dual-specificity phosphatase; glioblastoma; tumor promoting
01 Pubblicazione su rivista::01a Articolo in rivista
Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas / S., Messina; Frati, Luigi; C., Leonetti; C., Zuchegna; E., Di Zazzo; Calogero, Antonella; A., Porcellini. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - 30:35(2011), pp. 3813-3820. [10.1038/onc.2011.99]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/380017
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