Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1
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AbstractYC-1 has recently been demonstrated to have potent anti-invasion and anti-metastatic activity in several cancer models, in addition to its anti-proliferation activity. However, the mechanism underlying its anti-invasion/anti-metastatic activity is largely unknown. Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer in Southeast Asia. Here, we demonstrated that YC-1 inhibited invasiveness and proliferation of NPC cells, with the latter being accompanied by PARP cleavage, S-phase arrest and activation of Chk1/Chk2. We aimed at identifying novel anti-invasion mechanisms of YC-1 in NPC by a functional proteomic platform, the reverse phase protein array (RPPA). Our study revealed for the first time that multiple invasion-related signaling proteins (beta-catenin, caveolin, Src and EGFR), as well as several growth-related proteins (AMPK alpha, phospho-acetyl-CoA carboxylase (p-ACC), HER-2 and mTOR), which were previously un-described signaling proteins altered by YC-1, were found to be down-modulated by YC-1 in NPC cells. We hypothesized that YC-1-mediated downregulation of these invasion proteins contributed to its anti-invasion activity in NPC cells. Overexpression of EGFR, activated Src or caveolin, but not beta-catenin reversed the inhibitory effects of YC-1 on NPC cell invasion, with EGFR and activated Src having additional effects on rescuing NPC cells from YC-1-mediated growth inhibition. In summary, we have identified several novel anti-invasion mechanisms of YC-1 that could impact NPC, and possibly other cancers as well. (C) 2009 Published by Elsevier Inc.
All Author(s) ListHong B, Lui VWY, Hui EP, Lu YL, Leung HSY, Wong EYL, Cheng SH, Ng MHL, Mills GB, Chan ATC
Journal nameBiochemical Pharmacology
Volume Number79
Issue Number6
Pages842 - 852
LanguagesEnglish-United Kingdom
KeywordsAnti-invasion; Anti-proliferation; Nasopharyngeal carcinoma (NPC); Reverse phase protein array; YC-1 mechanisms
Web of Science Subject CategoriesPharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

Last updated on 2020-29-11 at 00:48