Role of IKKalpha in the EGFR Signaling Regulation
Annual summary rept. 15 Aug 2011-14 Aug 2012
M D ANDERSON CANCER CENTER HOUSTON TX
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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.
- Medicine and Medical Research