WIP and WICH/WIRE co-ordinately control invadopodium formation and maturation in human breast cancer cell invasion

Sci Rep. 2016 Mar 24:6:23590. doi: 10.1038/srep23590.

Abstract

Cancer cells form actin-rich degradative protrusions (invasive pseudopods and invadopodia), which allows their efficient dispersal during metastasis. Using biochemical and advanced imaging approaches, we demonstrate that the N-WASP-interactors WIP and WICH/WIRE play non-redundant roles in cancer cell invasion. WIP interacts with N-WASP and cortactin and is essential for invadopodium assembly, whereas WICH/WIRE regulates N-WASP activation to control invadopodium maturation and degradative activity. Our data also show that Nck interaction with WIP and WICH/WIRE modulates invadopodium maturation; changes in WIP and WICH/WIRE levels induce differential distribution of Nck. We show that WIP can replace WICH/WIRE functions and that elevated WIP levels correlate with high invasiveness. These findings identify a role for WICH/WIRE in invasiveness and highlight WIP as a hub for signaling molecule recruitment during invadopodium generation and cancer progression, as well as a potential diagnostic biomarker and an optimal target for therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cortactin / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Microfilament Proteins
  • Neoplasm Invasiveness
  • Podosomes / metabolism*
  • Signal Transduction
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism

Substances

  • CTTN protein, human
  • Carrier Proteins
  • Cortactin
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • WASL protein, human
  • WIPF1 protein, human
  • WIPF2 protein, human
  • Wiskott-Aldrich Syndrome Protein, Neuronal