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Article: Sox9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin

TitleSox9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin
Authors
Issue Date2016
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2016, v. 6, p. 32350:1-12 How to Cite?
AbstractThe cancer stem cell (CSC) hypothesis proposes a hierarchical organization of tumors, in which stem-like cells sustain tumors and drive metastasis. The molecular mechanisms underlying the acquisition of CSCs and metastatic traits are not well understood. SOX9 is a transcription factor linked to stem cell maintenance and commonly overexpressed in solid cancers including colorectal cancer. In this study, we show that SOX9 levels are higher in metastatic (SW620) than in primary colorectal cancer cells (SW480) derived from the same patient. This elevated expression correlated with enhanced self-renewal activity. By gain and loss-of-function studies in SW480 and SW620 cells respectively, we reveal that SOX9 levels modulate tumorsphere formation and self-renewal ability in vitro and tumor initiation in vivo. Moreover, SOX9 regulates migration and invasion and triggers the transition between epithelial and mesenchymal states. These activities are partially dependent on SOX9 post-transcriptional modifications. Importantly, treatment with rapamycin inhibits self-renewal and tumor growth in a SOX9- dependent manner. These results identify a functional role for SOX9 in regulating colorectal cancer cell plasticity and metastasis, and provide a strong rationale for a rapamycin-based therapeutic strategy.
Persistent Identifierhttp://hdl.handle.net/10722/234022
ISSN
2023 Impact Factor: 3.8
2023 SCImago Journal Rankings: 0.900
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCarrasco-Garcia, E-
dc.contributor.authorLopez, L-
dc.contributor.authorAldaz, P-
dc.contributor.authorArevalo, S-
dc.contributor.authorAldaregia, J-
dc.contributor.authorEgana, L-
dc.contributor.authorBujanda, L-
dc.contributor.authorCheung, MCH-
dc.contributor.authorSampron, N-
dc.contributor.authorGarcia, I-
dc.contributor.authorMatheu, A-
dc.date.accessioned2016-10-14T06:58:32Z-
dc.date.available2016-10-14T06:58:32Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, p. 32350:1-12-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/234022-
dc.description.abstractThe cancer stem cell (CSC) hypothesis proposes a hierarchical organization of tumors, in which stem-like cells sustain tumors and drive metastasis. The molecular mechanisms underlying the acquisition of CSCs and metastatic traits are not well understood. SOX9 is a transcription factor linked to stem cell maintenance and commonly overexpressed in solid cancers including colorectal cancer. In this study, we show that SOX9 levels are higher in metastatic (SW620) than in primary colorectal cancer cells (SW480) derived from the same patient. This elevated expression correlated with enhanced self-renewal activity. By gain and loss-of-function studies in SW480 and SW620 cells respectively, we reveal that SOX9 levels modulate tumorsphere formation and self-renewal ability in vitro and tumor initiation in vivo. Moreover, SOX9 regulates migration and invasion and triggers the transition between epithelial and mesenchymal states. These activities are partially dependent on SOX9 post-transcriptional modifications. Importantly, treatment with rapamycin inhibits self-renewal and tumor growth in a SOX9- dependent manner. These results identify a functional role for SOX9 in regulating colorectal cancer cell plasticity and metastasis, and provide a strong rationale for a rapamycin-based therapeutic strategy.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSox9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin-
dc.typeArticle-
dc.identifier.emailCheung, MCH: mcheung9@hkucc.hku.hk-
dc.identifier.authorityCheung, MCH=rp00245-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep32350-
dc.identifier.scopuseid_2-s2.0-84984669465-
dc.identifier.hkuros263360-
dc.identifier.volume6-
dc.identifier.spage32350:1-
dc.identifier.epage12-
dc.identifier.isiWOS:000391981800001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2045-2322-

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