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Article: A SIRT1-centered circuitry regulates breast cancer stemness and metastasis

TitleA SIRT1-centered circuitry regulates breast cancer stemness and metastasis
Authors
Issue Date2018
PublisherSpringer Nature [academic journals on nature.com]: Hybrid Journal. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2018, v. 37 n. 49, p. 6299-6315 How to Cite?
AbstractCancer stem cell (CSC)-dictated intratumor heterogeneity accounts for the majority of drug-resistance and distant metastases of breast cancers. Here, we identify a SIRT1-PRRX1-KLF4-ALDH1 circuitry, which couples CSCs, chemo-resistance, metastasis and aging. Pro-longevity protein SIRT1 deacetylates and stabilizes the epithelial-to-mesenchymal-transition (EMT) inducer PRRX1, which inhibits the transcription of core stemness factor KLF4. Loss of SIRT1 destabilizes PRRX1, disinhibits KLF4, and activates the transcription of ALDH1, which induces and functionally marks CSCs, resulting in chemo-resistance and metastatic relapse. Clinically, the level of PRRX1 is positively linked to SIRT1, whereas KLF4 is reversely correlated. Importantly, KLF4 inhibitor Kenpaullone sensitizes breast cancer cells and xenograft tumors to Paclitaxel and improves therapeutic effects. Our findings delineate a SIRT1-centered circuitry that regulates CSC origination, and targeting this pathway might be a promising therapeutic strategy. © 2018, The Author(s).
Persistent Identifierhttp://hdl.handle.net/10722/276211
ISSN
2017 Impact Factor: 6.854
2015 SCImago Journal Rankings: 4.047

 

DC FieldValueLanguage
dc.contributor.authorShi, L-
dc.contributor.authorTang, X-
dc.contributor.authorQian, M-
dc.contributor.authorLiu, Z-
dc.contributor.authorMeng, F-
dc.contributor.authorFu, L-
dc.contributor.authorWang, Z-
dc.contributor.authorZhu, WG-
dc.contributor.authorHuang, J-
dc.contributor.authorZhou, Z-
dc.contributor.authorLiu, B-
dc.date.accessioned2019-09-10T02:58:14Z-
dc.date.available2019-09-10T02:58:14Z-
dc.date.issued2018-
dc.identifier.citationOncogene, 2018, v. 37 n. 49, p. 6299-6315-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10722/276211-
dc.description.abstractCancer stem cell (CSC)-dictated intratumor heterogeneity accounts for the majority of drug-resistance and distant metastases of breast cancers. Here, we identify a SIRT1-PRRX1-KLF4-ALDH1 circuitry, which couples CSCs, chemo-resistance, metastasis and aging. Pro-longevity protein SIRT1 deacetylates and stabilizes the epithelial-to-mesenchymal-transition (EMT) inducer PRRX1, which inhibits the transcription of core stemness factor KLF4. Loss of SIRT1 destabilizes PRRX1, disinhibits KLF4, and activates the transcription of ALDH1, which induces and functionally marks CSCs, resulting in chemo-resistance and metastatic relapse. Clinically, the level of PRRX1 is positively linked to SIRT1, whereas KLF4 is reversely correlated. Importantly, KLF4 inhibitor Kenpaullone sensitizes breast cancer cells and xenograft tumors to Paclitaxel and improves therapeutic effects. Our findings delineate a SIRT1-centered circuitry that regulates CSC origination, and targeting this pathway might be a promising therapeutic strategy. © 2018, The Author(s).-
dc.languageeng-
dc.publisherSpringer Nature [academic journals on nature.com]: Hybrid Journal. The Journal's web site is located at http://www.nature.com/onc-
dc.relation.ispartofOncogene-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleA SIRT1-centered circuitry regulates breast cancer stemness and metastasis-
dc.typeArticle-
dc.identifier.emailHuang, J: jdhuang@hku.hk-
dc.identifier.emailZhou, Z: zhongjun@hku.hk-
dc.identifier.authorityHuang, J=rp00451-
dc.identifier.authorityZhou, Z=rp00503-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41388-018-0370-5-
dc.identifier.scopuseid_2-s2.0-85050396005-
dc.identifier.hkuros302534-
dc.identifier.volume37-
dc.identifier.issue49-
dc.identifier.spage6299-
dc.identifier.epage6315-
dc.publisher.placeUnited Kingdom-

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