Title:Role of Angiopoietin-like 4 (ANGPTL4), a Member of Matricellular Proteins: from Homeostasis to Inflammation and Cancer Metastasis
Volume: 2
Issue: 1
Author(s): Mintu Pal and Hari K. Koul
Affiliation:
Keywords:
Angiopoietin-like 4, angiogenesis, matricellular proteins, inflammation, cancer metastasis, tissue homeostasis.
Abstract: ANGPTL4 is a member of the angiopoietin/angiopoietin-like gene family and encodes a glycosylated, secreted
protein consisting of a signal sequence, N-terminal coiled-coil and a fibrinogen like C-terminal domain. The encoded protein
has emerged as a member of dynamically expressed, extracellular matrix-associated proteins that play critical roles in
regulating glucose homeostasis, lipid metabolism, and insulin sensitivity and also acts as an apoptosis survival factor for
vascular endothelial cells. Recent studies have uncovered novel ANGPTL4 activities unexpected for matricellular proteins,
including the ability to modulate integrin-mediated signaling and added a new facet to the cell-matrix interactions
and signaling during wound repair and cancer metastasis. ANGPTL4 function primarily through direct binding to specific
integrin receptors, thereby triggering signal transduction events that by modulating gene expression culminate in the regulation
of cell adhesion, migration, proliferation, differentiation and survival. This review surveys the published data on
molecular functions and mechanism by which ANGPTL4 exerts its effects. We also discuss use of ANGPTL4 as diagnostic
or prognostic marker for wound healing process and cancer; and highlight the therapeutic potential of this ligand, as
well as possible limitations to its use. We also consider the data on ANGPTL4 receptors and speculate on how to maximize
therapeutic benefit.