TY - JOUR
T1 - Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1
AU - Hong, Bo
AU - Lui, Vivian W.Y.
AU - Hui, Edwin P.
AU - Lu, Yiling
AU - Leung, Horasis S.Y.
AU - Wong, Elaine Y.L.
AU - Cheng, Suk Hang
AU - Ng, Margaret H.L.
AU - Mills, Gordon B.
AU - Chan, Anthony T.C.
N1 - Funding Information:
Thanks for the kind provision of pcDNA-HA-EGFR by Dr. Lan Ma (Fudan University, China). This study was supported by Research Grant Council, Hong Kong Government (CUHK4442/06M, to ATC Chan and EP Hui). Result of this study was presented in parts at AACR conferences: Molecular Targeting and Cancer Therapeutics, USA, 2007; Infection and Cancer: Biology, Therapeutics and Prevention, Hong Kong, 2008.
PY - 2010/3/15
Y1 - 2010/3/15
N2 - 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.
AB - 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.
KW - Anti-invasion
KW - Anti-proliferation
KW - Nasopharyngeal carcinoma (NPC)
KW - Reverse phase protein array
KW - YC-1 mechanisms
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U2 - 10.1016/j.bcp.2009.10.021
DO - 10.1016/j.bcp.2009.10.021
M3 - Article
C2 - 19879857
AN - SCOPUS:74249106458
SN - 0006-2952
VL - 79
SP - 842
EP - 852
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 6
ER -