Improving fascin inhibitors to block tumor cell migration and metastasis

Mol Oncol. 2016 Aug;10(7):966-80. doi: 10.1016/j.molonc.2016.03.006. Epub 2016 Apr 1.


Tumor metastasis is the major cause of mortality of cancer patients, being responsible for ∼90% of all cancer deaths. One of the key steps during tumor metastasis is tumor cell migration which requires actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are antenna-like filopodia. Fascin protein is the main actin-bundling protein in filopodia. Here we report the development of fascin-specific small-molecules that inhibit the interaction between fascin and actin. These inhibitors block the in vitro actin-binding and actin-bundling activities of fascin, tumor cell migration and tumor metastasis in mouse models. Mechanistically, these inhibitors likely occupy one of the actin-binding sites, reduce the binding of actin filaments, and thus lead to the inhibition of the bundling activity of fascin. At the cellular level, these inhibitors impair actin cytoskeletal reorganization. Our data indicate that target-specific anti-fascin agents will have great potential for treating metastatic tumors.

Keywords: Fascin; Inhibitors; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Animals
  • Breast Neoplasms / pathology*
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Disease Models, Animal
  • Female
  • Focal Adhesions / drug effects
  • Focal Adhesions / metabolism
  • Humans
  • Mice, Inbred BALB C
  • Microfilament Proteins / antagonists & inhibitors*
  • Microfilament Proteins / metabolism
  • Neoplasm Metastasis
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Stress Fibers / drug effects
  • Stress Fibers / metabolism


  • Carrier Proteins
  • FSCN1 protein, human
  • Microfilament Proteins
  • Small Molecule Libraries