How does fascin promote cancer metastasis?

FEBS J. 2021 Mar;288(5):1434-1446. doi: 10.1111/febs.15484. Epub 2020 Jul 23.

Abstract

Fascin is an F-actin-bundling protein that cross-links individual actin filaments into straight and stiff bundles. Fascin overexpression in cancer is strongly associated with poor prognosis and metastatic progression across different cancer types. It is well established that fascin plays a causative role in promoting metastatic progression. We will review the recent progress in our understanding of mechanisms underlying fascin-mediated cancer metastasis. This review will cover the biochemical basis for fascin-bundling activity, the mechanisms by which cancer cells upregulate fascin expression and the mechanism underlying fascin-mediated cancer cell migration, invasion, and metastatic colonization. We propose that fascin has broad roles in both metastatic dissemination and metastatic colonization. Understanding these mechanisms will be crucial to the development of anti-metastasis therapeutics targeting fascin.

Keywords: actin-bundling; cancer metastasis; fascin; metastatic colonization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / genetics*
  • Actin Cytoskeleton / metabolism
  • Actins / chemistry
  • Actins / genetics*
  • Actins / metabolism
  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplastic Cells, Circulating
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Signal Transduction
  • Transcription, Genetic
  • Tumor Microenvironment / genetics

Substances

  • Actins
  • Carrier Proteins
  • FSCN1 protein, human
  • Microfilament Proteins
  • Neoplasm Proteins
  • Protein Isoforms