Role of IKK-alpha in the EGFR Signaling Regulation

Abstract

Overexpression of EGFR is frequently linked to more aggressive tumor behavior, including increased proliferation, metastasis, and therapeutic resistance. Here, we identified a molecular linkage between IKK(alpha) and EGFR signaling in breast cancer cells. Inhibition of IKKs activity elevates EGFR tyrosine phosphorylation. In addition, IKK(alpha) forms a specific interaction with EGFR in Golgi apparatus and catalyzes EGFR S1026 phosphorylation. We found that EGFR S1026A possess a stronger tumorgenesis phenotype compare with wild type EGFR suggesting a negative regulation of IKK(alpha) in EGFR signaling. In agreement with an earlier finding where conditional ablation of IKK(alpha) in the mice keratinocytes elevates the autocrine loop of EGFR, our results further provide a potent role of IKK(alpha) kinase activity in preservation of EGFR activity.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2014
Accession Number
ADA612726

Entities

People

  • Chia-wei Li

Organizations

  • The University of Texas MD Anderson Cancer Center

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biology
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Movement
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Enzyme Inhibitors
  • Epithelial Cells
  • Health Services
  • Neoplasms
  • Oncology
  • Proteins
  • Therapy
  • United States

Readers

  • Breast cancer cell signaling and growth regulation.