Are Microtubules Involved in Anoikis

Abstract

This project is investigating the role of microtubule alterations in anoikis, with a view toward re-examining the mechanism of microtubule-targeting drugs such as taxol. During the past year, we have uncovered a new mechanism by which cell adhesion controls apoptosis. The death receptor adaptor protein FADD (FAS-associated death domain protein) is critical for anoikis as well as death ligand (e.g., FASL) - induced apoptosis. Recently, we discovered that FADD is primarily in the nucleus of attached cells, where it is unavailable for apoptosis induction. Detachment of mammary epithelial cells from extracellular matrix, however, provokes the export of FADD from the nucleus, thus promoting apoptosis. Our preliminary work suggests that microtubule drugs can promote FADD export, suggesting a new mechanism by which they can promote apoptosis. This is expected to have major ramifications for optimizing the use of taxol or other microtubule drugs in connection with other agents that may promote apoptosis.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2001
Accession Number
ADA397720

Entities

People

  • Steven M. Frisch

Organizations

  • Sanford Burnham Prebys Medical Discovery Institute

Tags

DTIC Thesaurus Topics

  • Adhesion
  • Albumins
  • Amino Acids
  • Apoptosis
  • Biomedical And Dental Materials
  • Carrier Proteins
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Culture Techniques
  • Cytoplasm
  • Cytoskeleton
  • Endothelial Cells
  • Epithelial Cells
  • Polymeric Films
  • Proteins

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.