GTSE1 is a microtubule plus-end tracking protein that regulates EB1-dependent cell migration

PLoS One. 2012;7(12):e51259. doi: 10.1371/journal.pone.0051259. Epub 2012 Dec 7.

Abstract

The regulation of cell migration is a highly complex process that is often compromised when cancer cells become metastatic. The microtubule cytoskeleton is necessary for cell migration, but how microtubules and microtubule-associated proteins regulate multiple pathways promoting cell migration remains unclear. Microtubule plus-end binding proteins (+TIPs) are emerging as important players in many cellular functions, including cell migration. Here we identify a +TIP, GTSE1, that promotes cell migration. GTSE1 accumulates at growing microtubule plus ends through interaction with the EB1+TIP. The EB1-dependent +TIP activity of GTSE1 is required for cell migration, as well as for microtubule-dependent disassembly of focal adhesions. GTSE1 protein levels determine the migratory capacity of both nontransformed and breast cancer cell lines. In breast cancers, increased GTSE1 expression correlates with invasive potential, tumor stage, and time to distant metastasis, suggesting that misregulation of GTSE1 expression could be associated with increased invasive potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line
  • Cell Movement / physiology*
  • DNA Primers / genetics
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunoprecipitation
  • Kaplan-Meier Estimate
  • Mass Spectrometry
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Microtubules / physiology*
  • Neoplasm Invasiveness / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction

Substances

  • DNA Primers
  • GTSE1 protein, human
  • MAPRE1 protein, human
  • Microtubule-Associated Proteins
  • RNA, Small Interfering

Associated data

  • GEO/GSE11121
  • GEO/GSE12093
  • GEO/GSE1456
  • GEO/GSE16446
  • GEO/GSE19615
  • GEO/GSE20685
  • GEO/GSE21653
  • GEO/GSE2603
  • GEO/GSE4922
  • GEO/GSE5327
  • GEO/GSE6532
  • GEO/GSE7390

Grant support

Work done in CS’s lab at Laboratorio Nazionale The Interuniversity Consortium for Biotechnology has been supported by Italian Association for Cancer Research (AIRC) IG-2010 and AIRC Special Program Molecular Clinical Oncology “5 per mille”. MS and LP were supported by fellowships from Area Science Park. YC is supported by a PhD Fellowship from the School of Molecular Biomedicine University of Trieste. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.