Mitotic perturbations frequently lead to chromosome mis-segregation that generates genome instability, thereby triggering tumor onset and/or progression. Error-free mitosis depends on fidelity-monitoring systems that ensure the temporal and spatial coordination of chromosome segregation. Recent investigations are focused on mitotic DNA damage response (DDR) and chromosome mis-segregations with the aim of developing more efficient anti-cancer therapies. We previously demonstrated that trichoplein keratin filament binding protein (TpMs) exhibits hallmarks of a tumor suppressor gene in cancer-derived cells and human tumors. Here, we show that silencing of TpMs expression results in chromosome mis-segregation, DNA damage and chromosomal instability. TpMs interacts with Mad2, and TpMs depletion results in decreased levels of Mad2 and Cyclin B1 proteins. All the genetic alterations observed are consistent with both defective activation of the spindle assembly checkpoint and mitotic progression. Thus, low levels of TpMs found in certain human tumors may contribute to cellular transformation by promoting genomic instability.

Depletion of Trichoplein (TpMs) Causes Chromosome Mis-Segregation, DNA Damage and Chromosome Instability in Cancer Cells / Lauriola, Angela; Martello, Andrea; Fantini, Sebastian; Marverti, Gaetano; Zanocco-Marani, Tommaso; Davalli, Pierpaola; Guardavaccaro, Daniele; Mai, Sabine; Caporali, Andrea; D’Arca, Domenico. - In: CANCERS. - ISSN 2072-6694. - 12:4(2020), pp. 993-1008. [10.3390/cancers12040993]

Depletion of Trichoplein (TpMs) Causes Chromosome Mis-Segregation, DNA Damage and Chromosome Instability in Cancer Cells

Lauriola, Angela;Martello, Andrea;Fantini, Sebastian;Marverti, Gaetano;Zanocco-Marani, Tommaso;Davalli, Pierpaola;D’Arca, Domenico
2020

Abstract

Mitotic perturbations frequently lead to chromosome mis-segregation that generates genome instability, thereby triggering tumor onset and/or progression. Error-free mitosis depends on fidelity-monitoring systems that ensure the temporal and spatial coordination of chromosome segregation. Recent investigations are focused on mitotic DNA damage response (DDR) and chromosome mis-segregations with the aim of developing more efficient anti-cancer therapies. We previously demonstrated that trichoplein keratin filament binding protein (TpMs) exhibits hallmarks of a tumor suppressor gene in cancer-derived cells and human tumors. Here, we show that silencing of TpMs expression results in chromosome mis-segregation, DNA damage and chromosomal instability. TpMs interacts with Mad2, and TpMs depletion results in decreased levels of Mad2 and Cyclin B1 proteins. All the genetic alterations observed are consistent with both defective activation of the spindle assembly checkpoint and mitotic progression. Thus, low levels of TpMs found in certain human tumors may contribute to cellular transformation by promoting genomic instability.
2020
17-apr-2020
12
4
993
1008
Depletion of Trichoplein (TpMs) Causes Chromosome Mis-Segregation, DNA Damage and Chromosome Instability in Cancer Cells / Lauriola, Angela; Martello, Andrea; Fantini, Sebastian; Marverti, Gaetano; Zanocco-Marani, Tommaso; Davalli, Pierpaola; Guardavaccaro, Daniele; Mai, Sabine; Caporali, Andrea; D’Arca, Domenico. - In: CANCERS. - ISSN 2072-6694. - 12:4(2020), pp. 993-1008. [10.3390/cancers12040993]
Lauriola, Angela; Martello, Andrea; Fantini, Sebastian; Marverti, Gaetano; Zanocco-Marani, Tommaso; Davalli, Pierpaola; Guardavaccaro, Daniele; Mai, Sabine; Caporali, Andrea; D’Arca, Domenico
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1201284
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