Inhibitor of growth 4 suppresses cell spreading and cell migration by interacting with a novel binding partner, liprin α

Jiang Cheng Shen, Motoko Unoki, Damien Ythier, Alain Duperray, Lyuba Varticovski, Kensuke Kumamoto, Remy Pedeux, Curtis C. Harris

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

Inhibitor of growth 4 (ING4) is a candidate tumor suppressor that plays a major role in gene regulation, cell cycle control, apoptosis, and angiogenesis. ING4 expression is down-regulated in glioblastoma cells and head and neck squamous cell carcinoma. Here, we identified liprin α1/PPFIA1, a cytoplasmic protein necessary for focal adhesion formation and axon guidance, as a novel interacting protein with ING4. ING4 and liprin α1 colocalized at lamellipodia in the vicinity of vinculin. Overexpressed ING4 suppressed cell spreading and cell migration. In contrast, overexpressed liprin α1 enhanced cell spreading and cell migration. Knockdown of endogenous ING4 with RNA interference induced cell motility, whereas knockdown of endogenous liprin α1 suppressed cell motility. ING4 also suppressed cell motility that was enhanced by liprin al. However, ING4 did not further suppress cell motility when liprin α1 was suppressed with RNA interference, suggesting a functional and mechanistic interdependence between these proteins. In addition to its nuclear functions, cytoplasmic ING4 interacts with liprin α1 to regulate cell migration and, with its known antiangiogenic function, may prevent invasion and metastasis.

Original languageEnglish
Pages (from-to)2552-2558
Number of pages7
JournalCancer Research
Volume67
Issue number6
DOIs
Publication statusPublished - Mar 15 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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