Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1

Bo Hong, Vivian W.Y. Lui, Edwin P. Hui, Yiling Lu, Horasis S.Y. Leung, Elaine Y.L. Wong, Suk Hang Cheng, Margaret H.L. Ng, Gordon B. Mills, Anthony T.C. Chan

    Research output: Contribution to journalArticle

    16 Scopus citations


    YC-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 (β-catenin, caveolin, Src and EGFR), as well as several growth-related proteins (AMPKα, 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 β-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.

    Original languageEnglish (US)
    Pages (from-to)842-852
    Number of pages11
    JournalBiochemical Pharmacology
    Issue number6
    StatePublished - Mar 15 2010


    • Anti-invasion
    • Anti-proliferation
    • Nasopharyngeal carcinoma (NPC)
    • Reverse phase protein array
    • YC-1 mechanisms

    ASJC Scopus subject areas

    • Biochemistry
    • Pharmacology

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    Hong, B., Lui, V. W. Y., Hui, E. P., Lu, Y., Leung, H. S. Y., Wong, E. Y. L., Cheng, S. H., Ng, M. H. L., Mills, G. B., & Chan, A. T. C. (2010). Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1. Biochemical Pharmacology, 79(6), 842-852.