RABGTPases in MT1-MMP trafficking and cell invasion: Physiology versus pathology

Small GTPases. 2015;6(3):145-52. doi: 10.4161/21541248.2014.985484. Epub 2015 Jun 24.


The matrix metalloproteinase MT1-MMP is a central regulator of cell invasion in both physiological and pathological settings, such as tissue surveillance by immune cells and cancer cell metastasis. MT1-MMP cleaves a plethora of intra- and extracellular proteins, including extracellular matrix proteins, matrix receptors, and also other MMPs, and thus enables modification of both the cell surface proteome and the pericellular environment. Despite its importance for cell invasion, the pathways regulating MT1-MMP exposure on the cell surface are largely unknown. Recently, our groups discovered that a specific subset of RABGTPases, most notably RAB5a, is critical for MT1-MMP trafficking in primary human macrophages and carcinoma cells. Here, we discuss and contrast our findings for both cell types, pointing out common features and differences in the RABGTPase-dependent trafficking of MT1-MMP in health and disease.

Keywords: MT1-MMP; RABGTPases; carcinoma cells; cell invasion; intracellular trafficking; invadopodia; macrophages; podosomes; vesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cell Movement
  • Cells, Cultured
  • Extracellular Matrix / metabolism
  • Humans
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Matrix Metalloproteinase 14 / metabolism*
  • Neoplasm Invasiveness
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Transport
  • rab GTP-Binding Proteins / metabolism*


  • MMP14 protein, human
  • Matrix Metalloproteinase 14
  • rab GTP-Binding Proteins