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 Mills, Anthony T.C. Chan

Research output: Contribution to journalArticle

15 Citations (Scopus)

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

Fingerprint

Protein Array Analysis
Caveolins
Catenins
Proteins
Acetyl-CoA Carboxylase
AMP-Activated Protein Kinases
Chemical activation
Southeastern Asia
Nasopharyngeal carcinoma
Head and Neck Neoplasms
Growth
S Phase
Proteomics
Neoplasms
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Hong, B., Lui, V. W. Y., Hui, E. P., Lu, Y., Leung, H. S. Y., Wong, E. Y. L., ... Chan, A. T. C. (2010). Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1. Biochemical Pharmacology, 79(6), 842-852. https://doi.org/10.1016/j.bcp.2009.10.021

Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1. / Hong, Bo; Lui, Vivian W.Y.; Hui, Edwin P.; Lu, Yiling; Leung, Horasis S.Y.; Wong, Elaine Y.L.; Cheng, Suk Hang; Ng, Margaret H.L.; Mills, Gordon; Chan, Anthony T.C.

In: Biochemical Pharmacology, Vol. 79, No. 6, 15.03.2010, p. 842-852.

Research output: Contribution to journalArticle

Hong, B, Lui, VWY, Hui, EP, Lu, Y, Leung, HSY, Wong, EYL, Cheng, SH, Ng, MHL, Mills, G & Chan, ATC 2010, 'Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1', Biochemical Pharmacology, vol. 79, no. 6, pp. 842-852. https://doi.org/10.1016/j.bcp.2009.10.021
Hong, Bo ; Lui, Vivian W.Y. ; Hui, Edwin P. ; Lu, Yiling ; Leung, Horasis S.Y. ; Wong, Elaine Y.L. ; Cheng, Suk Hang ; Ng, Margaret H.L. ; Mills, Gordon ; Chan, Anthony T.C. / Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1. In: Biochemical Pharmacology. 2010 ; Vol. 79, No. 6. pp. 842-852.
@article{b43a632047ae40159ee5e6d750c33e42,
title = "Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1",
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.",
keywords = "Anti-invasion, Anti-proliferation, Nasopharyngeal carcinoma (NPC), Reverse phase protein array, YC-1 mechanisms",
author = "Bo Hong and Lui, {Vivian W.Y.} and Hui, {Edwin P.} and Yiling Lu and Leung, {Horasis S.Y.} and Wong, {Elaine Y.L.} and Cheng, {Suk Hang} and Ng, {Margaret H.L.} and Gordon Mills and Chan, {Anthony T.C.}",
year = "2010",
month = "3",
day = "15",
doi = "10.1016/j.bcp.2009.10.021",
language = "English (US)",
volume = "79",
pages = "842--852",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "6",

}

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

AU - Chan, Anthony T.C.

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

UR - http://www.scopus.com/inward/record.url?scp=74249106458&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74249106458&partnerID=8YFLogxK

U2 - 10.1016/j.bcp.2009.10.021

DO - 10.1016/j.bcp.2009.10.021

M3 - Article

C2 - 19879857

AN - SCOPUS:74249106458

VL - 79

SP - 842

EP - 852

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 6

ER -