Role of IKK-alpha in EGFR Signaling Regulation
Annual rept. 15 Aug 2012-14 Aug 2013
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 IKK 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 IKK in the mice keratinocytes elevates the autocrine loop of EGFR, our results further provide a potent role of IKK kinase activity in preservation of EGFR activity.
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