Cited 14 times in
A Functional Signature Ontology (FUSION) screen detects an AMPK inhibitor with selective toxicity toward human colon tumor cells
DC Field | Value | Language |
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dc.contributor.author | 김현석 | - |
dc.date.accessioned | 2018-08-28T17:05:58Z | - |
dc.date.available | 2018-08-28T17:05:58Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/162251 | - |
dc.description.abstract | AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing alpha and regulatory beta and gamma subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKalpha1 expression is relatively consistent across colon cancer cell lines, AMPKalpha1 depletion does not induce cell death. Conversely, AMPKalpha2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. We used Functional Signature Ontology (FUSION) to screen a natural product library to identify compounds that were inhibitors of AMPK to test its potential for detecting small molecules with preferential toxicity toward human colon tumor cells. FUSION identified 5'-hydroxy-staurosporine, which competitively inhibits AMPK. Human colon cancer cell lines are notably more sensitive to 5'-hydroxy-staurosporine than are non-transformed human colon epithelial cells. This study serves as proof-of-concept for unbiased FUSION-based detection of small molecule inhibitors of therapeutic targets and highlights its potential to identify novel compounds for cancer therapy development. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | A Functional Signature Ontology (FUSION) screen detects an AMPK inhibitor with selective toxicity toward human colon tumor cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Life Science | - |
dc.contributor.googleauthor | Binita Das | - |
dc.contributor.googleauthor | Beth K Neilsen | - |
dc.contributor.googleauthor | Kurt W Fisher | - |
dc.contributor.googleauthor | Drew Gehring | - |
dc.contributor.googleauthor | Youcai Hu | - |
dc.contributor.googleauthor | Deanna J Volle | - |
dc.contributor.googleauthor | Hyun Seok Kim | - |
dc.contributor.googleauthor | Jamie L McCall | - |
dc.contributor.googleauthor | David L Kelly | - |
dc.contributor.googleauthor | John B MacMillan | - |
dc.contributor.googleauthor | Michael A White | - |
dc.contributor.googleauthor | Robert E Lewis | - |
dc.identifier.doi | 10.1038/s41598-018-22090-6 | - |
dc.contributor.localId | A01111 | - |
dc.relation.journalcode | J02646 | - |
dc.identifier.eissn | 2045-2322 | - |
dc.identifier.pmid | 29491475 | - |
dc.contributor.alternativeName | Kim, Hyun Seok | - |
dc.contributor.affiliatedAuthor | Kim, Hyun Seok | - |
dc.citation.volume | 8 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 3770 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, Vol.8(1) : 3770, 2018 | - |
dc.identifier.rimsid | 59837 | - |
dc.type.rims | ART | - |
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