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 journalArticlepeer-review

16 Scopus citations

Abstract

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
Volume79
Issue number6
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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