The granulin gene family: from cancer to dementia

Bioessays. 2009 Nov;31(11):1245-54. doi: 10.1002/bies.200900086.

Abstract

The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine-rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dementia / genetics
  • Frontal Lobe / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inflammation
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Models, Molecular
  • Multigene Family
  • Neoplasms / genetics
  • Neurodegenerative Diseases / genetics
  • Progranulins
  • Wound Healing

Substances

  • Intercellular Signaling Peptides and Proteins
  • Progranulins