RhoGTPase Involvement in Breast Cancer Migration and Invasion

Abstract

Using a high throughput small interfering RNA approach (siRNA) I screened 1081 human genes (kinases, phosphatases and a library of migration and adhesion related genes) using an automated wound healing assay to identify genes that regulate cell migration using the normal mammary epithelial cell line MCF10A. After extensive validation using other siRNAs and shRNAs I identified 66 High Confidence (HC) genes that Accelerate or Inhibit cell motility. Of these genes, 42 have no prior association with cell motility or adhesion and of these, 12 are uncharacterized with respect to any biological process. The migration pattern for the 66 HC genes were established using time-lapse video microscopy and revealed that a significant proportion of the genes that accelerate migration do so by disruption of cell-cell adhesion and adoption of highly erratic and random cell motility. These represent novel targets for future studies relating to breast carcinoma progression.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2008
Accession Number
ADA482528

Entities

People

  • Kaylene J. Simpson

Organizations

  • Harvard Medical School

Tags

DTIC Thesaurus Topics

  • Adhesion
  • Breast Cancer
  • Cell Line
  • Cell Membrane Structures
  • Cell Movement
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Cytoskeleton
  • Epithelial Cells
  • Microscopy
  • Neoplasms
  • Throughput
  • Validation
  • Wound Healing

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and genetic basis of cancer.
  • Systems Analysis and Design