Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth

Cancer Res. 2017 Oct 1;77(19):5301-5312. doi: 10.1158/0008-5472.CAN-17-0418. Epub 2017 Aug 14.

Abstract

Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here, we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell-cycle progression and tumor growth in vivo Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1-regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through posttranslational modification. These findings provide important new insights into the role of FAK as a scaffolding protein in molecular complexes that regulate gene transcription. Cancer Res; 77(19); 5301-12. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Proliferation
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Focal Adhesion Protein-Tyrosine Kinases / physiology*
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Nude
  • Phosphorylation
  • Signal Transduction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Insulin-Like Growth Factor Binding Protein 3
  • Runx1 protein, mouse
  • Focal Adhesion Protein-Tyrosine Kinases