Role of IKKalpha 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 IKKalpha and EGFR signaling in breast cancer cells. Inhibition of IKKs activity elevates EGFR tyrosine phosphorylation. In addition, IKK! 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! in EGFR signaling. In agreement with an earlier finding where conditional ablation of IKKalpha in the mice Keratinocytes elevates the autocrine loop of EGFR, our results further provide a potent role of IKKalpha kinase activity in preservation of EGFR activity.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2011
Accession Number
ADA610026

Entities

People

  • Chia-wei Li

Organizations

  • The University of Texas MD Anderson Cancer Center

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Golgi Apparatus
  • Inhibition
  • Kinases
  • Mammary Glands
  • Neoplasms
  • Phosphorylation
  • Proteins
  • Regulations
  • Tyrosine

Readers

  • Breast cancer cell signaling and growth regulation.