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

TitleReverse phase protein array identifies novel anti-invasion mechanisms of YC-1
Authors
Issue Date2010
Citation
Biochemical Pharmacology, 2010, v. 79 n. 6, p. 842-852 How to Cite?
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 (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. © 2009.
Persistent Identifierhttp://hdl.handle.net/10722/194507
ISSN
2015 Impact Factor: 5.091
2015 SCImago Journal Rankings: 2.263
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHong, B-
dc.contributor.authorLui, VWY-
dc.contributor.authorHui, EP-
dc.contributor.authorLu, Y-
dc.contributor.authorLeung, HSY-
dc.contributor.authorWong, EYL-
dc.contributor.authorCheng, S-H-
dc.contributor.authorNg, MHL-
dc.contributor.authorMills, GB-
dc.contributor.authorChan, ATC-
dc.date.accessioned2014-01-30T03:32:40Z-
dc.date.available2014-01-30T03:32:40Z-
dc.date.issued2010-
dc.identifier.citationBiochemical Pharmacology, 2010, v. 79 n. 6, p. 842-852-
dc.identifier.issn0006-2952-
dc.identifier.urihttp://hdl.handle.net/10722/194507-
dc.description.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 (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. © 2009.-
dc.languageeng-
dc.relation.ispartofBiochemical Pharmacology-
dc.titleReverse phase protein array identifies novel anti-invasion mechanisms of YC-1-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2009.10.021-
dc.identifier.pmid19879857-
dc.identifier.scopuseid_2-s2.0-74249106458-
dc.identifier.volume79-
dc.identifier.issue6-
dc.identifier.spage842-
dc.identifier.epage852-
dc.identifier.isiWOS:000274165500005-

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