HEI10 negatively regulates cell invasion by inhibiting cyclin B/Cdk1 and other promotility proteins

Mahendra Singh, E. Nicolas, W. Gherraby, D. Dadke, S. Lessin, E. A. Golemis

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Human enhancer of invasion, clone 10 (HEI10) (CCNB1IP1) was first described as a RING-finger family ubiquitin ligase that regulates cell cycle by interacting with cyclin B and promoting its degradation. Subsequently, other studies suggested specific upregulation of HEI10 in metastatic melanoma and demonstrated direct interaction between HEI10 and the tumor suppressor Merlin, encoded by the neurofibromatosis 2 gene. These and other results led us to hypothesize that HEI10 also influences the processes of cell migration and metastasis. We here show that cells with depleted HEI10 both migrate more rapidly and invade more effectively than control cells. HEI10 depletion post-transcriptionally increases the expression of a group of promotility regulatory proteins including p130Cas, paxillin, Cdk1 and cyclin B2, but excluding Merlin. Among these, only inhibition of Cdk1/cyclin B activity specifically reversed the motility and invasion of HEI10-depleted cells. Finally, HEI10 is abundantly transcribed in many human tissues, and particularly abundant in some tumor cell lines, suggesting that it may be commonly involved in coordinating cell cycle with cell migration and invasion.

Original languageEnglish (US)
Pages (from-to)4825-4832
Number of pages8
JournalOncogene
Volume26
Issue number33
DOIs
StatePublished - Jul 19 2007
Externally publishedYes

Fingerprint

Cyclin B
Clone Cells
Proteins
Neurofibromin 2
Cell Movement
Cyclin B2
Cell Cycle
Neurofibromatosis 2 Genes
Crk-Associated Substrate Protein
Paxillin
Ligases
Ubiquitin
Tumor Cell Line
Fingers
Melanoma
Up-Regulation
Neoplasm Metastasis

Keywords

  • Cdk1
  • Cell cycle
  • Cyclin B
  • HEI10
  • Invasion
  • Migration

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

HEI10 negatively regulates cell invasion by inhibiting cyclin B/Cdk1 and other promotility proteins. / Singh, Mahendra; Nicolas, E.; Gherraby, W.; Dadke, D.; Lessin, S.; Golemis, E. A.

In: Oncogene, Vol. 26, No. 33, 19.07.2007, p. 4825-4832.

Research output: Contribution to journalArticle

Singh, M, Nicolas, E, Gherraby, W, Dadke, D, Lessin, S & Golemis, EA 2007, 'HEI10 negatively regulates cell invasion by inhibiting cyclin B/Cdk1 and other promotility proteins', Oncogene, vol. 26, no. 33, pp. 4825-4832. https://doi.org/10.1038/sj.onc.1210282
Singh, Mahendra ; Nicolas, E. ; Gherraby, W. ; Dadke, D. ; Lessin, S. ; Golemis, E. A. / HEI10 negatively regulates cell invasion by inhibiting cyclin B/Cdk1 and other promotility proteins. In: Oncogene. 2007 ; Vol. 26, No. 33. pp. 4825-4832.
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