Highly Expressed in Cancer protein 1 (Hec1) is a subunit of the Ndc80 complex, a constituent of the mitotic kinetochore. HEC1 has been shown to be overexpressed in many cancers, suggesting that HEC1 upregulation is involved in the generation and/or maintenance of the tumour phenotype. However, the regulation of Hec1 expression in normal and tumour cells and the molecular alterations promoting accumulation of this protein in cancer cells are still unknown. Here we show that elevated Hec1 protein levels are characteristic of transformed cell lines of different origins and that kinetochore recruitment of this protein is also increased in cancer cell lines in comparison with normal human cells. Using different cell synchronization strategies, Hec1 expression was found to be tightly regulated during the cell cycle in both normal and cancer cells. A limited proteasome-dependent degradation of Hec1 cellular content was observed at mitotic exit, with no evident differences between normal and cancer cells. Interestingly, increased expression of HEC1 mRNA and Hec1 protein was observed after transient silencing of the retinoblastoma gene by siRNA or following microRNA-mediated permanent depletion of the retinoblastoma protein in HCT116 cells. Our data provide evidence for a functional link between Hec1 expression and the pRb pathway. These observations suggest that disruption of pRb function may lead to chromosome segregation errors and mitotic defects through Hec1 overexpression. This may importantly contribute to aneuploidy and chromosomal instability in RB-defective cancer cells.

Ferretti, C., Totta, P., Fiore, M., Mattiuzzo, M., Schillaci, T., Ricordy, R., et al. (2010). Expression of the kinetochore protein Hec1 during the cell cycle in normal and cancer cells and its regulation by the pRb pathway. CELL CYCLE, 9(20), 4174-4182 [10.4161/cc].

Expression of the kinetochore protein Hec1 during the cell cycle in normal and cancer cells and its regulation by the pRb pathway.

SCHILLACI, Tiziana;DI LEONARDO, Aldo;
2010

Abstract

Highly Expressed in Cancer protein 1 (Hec1) is a subunit of the Ndc80 complex, a constituent of the mitotic kinetochore. HEC1 has been shown to be overexpressed in many cancers, suggesting that HEC1 upregulation is involved in the generation and/or maintenance of the tumour phenotype. However, the regulation of Hec1 expression in normal and tumour cells and the molecular alterations promoting accumulation of this protein in cancer cells are still unknown. Here we show that elevated Hec1 protein levels are characteristic of transformed cell lines of different origins and that kinetochore recruitment of this protein is also increased in cancer cell lines in comparison with normal human cells. Using different cell synchronization strategies, Hec1 expression was found to be tightly regulated during the cell cycle in both normal and cancer cells. A limited proteasome-dependent degradation of Hec1 cellular content was observed at mitotic exit, with no evident differences between normal and cancer cells. Interestingly, increased expression of HEC1 mRNA and Hec1 protein was observed after transient silencing of the retinoblastoma gene by siRNA or following microRNA-mediated permanent depletion of the retinoblastoma protein in HCT116 cells. Our data provide evidence for a functional link between Hec1 expression and the pRb pathway. These observations suggest that disruption of pRb function may lead to chromosome segregation errors and mitotic defects through Hec1 overexpression. This may importantly contribute to aneuploidy and chromosomal instability in RB-defective cancer cells.
Settore BIO/18 - Genetica
Ferretti, C., Totta, P., Fiore, M., Mattiuzzo, M., Schillaci, T., Ricordy, R., et al. (2010). Expression of the kinetochore protein Hec1 during the cell cycle in normal and cancer cells and its regulation by the pRb pathway. CELL CYCLE, 9(20), 4174-4182 [10.4161/cc].
File in questo prodotto:
File Dimensione Formato  
FerrettiCC9-20.pdf

Solo gestori archvio

Dimensione 1.47 MB
Formato Adobe PDF
1.47 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/51423
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 23
social impact