Improving fascin inhibitors to block tumor cell migration and metastasis. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • April 1, 2016

Research

keywords

  • Breast Neoplasms
  • Carrier Proteins
  • Cell Movement
  • Microfilament Proteins

Identity

PubMed Central ID

  • PMC5423182

Scopus Document Identifier

  • 84963566233

Digital Object Identifier (DOI)

  • 10.1016/j.molonc.2016.03.006

PubMed ID

  • 27071719

Additional Document Info

volume

  • 10

issue

  • 7