Targeting WASF3 Signaling in Metastatic Cancer

Int J Mol Sci. 2021 Jan 15;22(2):836. doi: 10.3390/ijms22020836.

Abstract

Increasing evidence indicates that cancer metastasis is regulated by specific genetic pathways independent of those controlling tumorigenesis and cancer growth. WASF3, a Wiskott-Aldrich syndrome protein family member, appears to play a major role not only in the regulation of actin cytoskeleton dynamics but also in cancer cell invasion/metastasis. Recent studies have highlighted that WASF3 is a master regulator and acts as a pivotal scaffolding protein, bringing the various components of metastatic signaling complexes together both spatially and temporally. Herein, targeting WASF3 at the levels of transcription, protein stability, and phosphorylation holds great promise for metastasis suppression, regardless of the diverse genetic backgrounds associated with tumor development. This review focuses on the critical and distinct contributions of WASF3 in the regulation of signal pathways promoting cancer cell invasion and metastasis.

Keywords: WASF3; cancer; drug target; metastasis; signaling network.

Publication types

  • Review

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Animals
  • Cell Movement
  • Endoplasmic Reticulum Chaperone BiP
  • Gene Expression Regulation, Neoplastic*
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Janus Kinase 2 / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • MicroRNAs / metabolism
  • Mitochondrial Proteins / metabolism
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis*
  • Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Wiskott-Aldrich Syndrome Protein Family / metabolism*

Substances

  • ATAD3A protein, human
  • Endoplasmic Reticulum Chaperone BiP
  • HIF1A protein, human
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins
  • MicroRNAs
  • Mitochondrial Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • WASF3 protein, human
  • Wasf3 protein, mouse
  • Wiskott-Aldrich Syndrome Protein Family
  • JAK2 protein, human
  • Janus Kinase 2
  • ATPases Associated with Diverse Cellular Activities