We used an extensive collection of HNSCC samples to demonstrate that elevated
levels of AEG-1 protein are associated with lymph node metastasis and poor
prognosis in HNSCC patients. AEG-1 primarily acts through the NF-κB pathway, by
enhancing phosphorylation on serine 536 of RelA, which in turn results in an
increased expression of MMP1. These findings may support the development of
AEG-1-targeting therapeutics, such as small molecules, interference RNA with
suitable drug delivering system or DNA vaccine, [121] to bolster our arsenal of
adjuvant chemotherapy, thereby improving the clinical outcome of HNSCC patients
with high AEG-1 expression. In the meantime, elucidation of physiological function
of AEG-1 through transgenic murine models and large-scale screening of the
expression status of AEG-1 in normal human tissue are required to minimize the
potential side effect.
Acknowledgements
We thank the Core Facility of the Institute of Cellular and Organismic Biology,
the Microarray Core Facility of the Institute of Molecular Biology, and the National
RNAi Core Facility, Academia Sinica for their generous and proficient technical
support.
Funding
The current study was supported by the National Science Council, Taiwan,
Grants NSC101-2325-B-001-010 and NSC101-2321-B-001-021 (to Han-Chung Wu),
start-up funding for new faculty, National Taiwan university, Taipei, Taiwan,
No.98R0616 and Professor Kwan’s foundation, Taipei, Taiwan (to Yi-Ping Wang).
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