How does a protein with dual mitotic spindle and extracellular matrix receptor functions affect tumor susceptibility and progression?

Patrick G. Telmer, Cornelia Tolg, James B. McCarthy, Eva A. Turley

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The mechanisms responsible for the oncogenic effects of the hyaluronan (HA) receptor and mitotic spindle binding protein, RHAMM, are poorly understood. On one hand, extracellular RHAMM interacts with HA and cellsurface receptors such as CD44 to coordinately activate the MAPK/ERK1,2 pathway, thus contributing to the spread and proliferation of tumor cells. On the other hand, intracellular RHAMM decorates mitotic spindles and is necessary for spindle formation and progression through G 2/M and overexpression or loss of RHAMM can result in multipole spindles and chromosome missegregation. The deregulation of these intracellular functions could lead to genomic instability and fuel tumor progression. This suggests that both extracellular and intracellular RHAMM can promote tumor progression. Intracellular RHAMM can bind directly to ERK1 to form complexes with ERK2, MEK1 and ERK1,2 substrates, and we present a model whereby RHAMM's function is as a scaffold protein, controlling activation and targeting of ERK1,2 to specific substrates.

Original languageEnglish (US)
Pages (from-to)182-185
Number of pages4
JournalCommunicative and Integrative Biology
Volume4
Issue number2
DOIs
StatePublished - Mar 2011

Keywords

  • CD168
  • Cancer biology
  • Cell cycle
  • Cell migration
  • Hmmr
  • MAPK
  • Mitosis
  • Rhamm

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