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Article: Chemotherapy‐Enriched THBS2‐Deficient Cancer Stem Cells Drive Hepatocarcinogenesis through Matrix Softness Induced Histone H3 Modifications

TitleChemotherapy‐Enriched THBS2‐Deficient Cancer Stem Cells Drive Hepatocarcinogenesis through Matrix Softness Induced Histone H3 Modifications
Authors
KeywordsCancer stemness
CD133
Hepatocellular carcinomas
Histone modifications
Matrix stiffness
Mechanoepigenetics
Metastasis
THBS2
Issue Date2021
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844
Citation
Advanced Science, 2021, v. 8 n. 5, article no. 2002483 How to Cite?
AbstractThe physical microenvironment is a critical mediator of tumor behavior. However, detailed biological and mechanistic insight is lacking. The present study reveals the role of chemotherapy-enriched CD133+ liver cancer stem cells (CSCs) with THBS2 deficiency. This subpopulation of cells contributes to a more aggressive cancer and functional stemness phenotype in hepatocellular carcinoma (HCC) by remodeling the extracellular matrix (ECM) through the regulation of matrix metalloproteinase (MMP) activity, collagen degradation, and matrix stiffness. The local soft spots created by these liver CSCs can enhance stemness and drug resistance and provide a route of escape to facilitate HCC metastasis. Interestingly, a positive feed-forward loop is identified where a local soft spot microenvironment in the HCC tumor is enriched with CD133 expressing cells that secrete markedly less ECM-modifying THBS2 upon histone H3 modification at its promoter region, allowing the maintenance of a localized soft spot matrix. Clinically, THBS2 deficiency is also correlated with low HCC survival, where high levels of CSCs with low THBS2 expression in HCC are associated with decreased collagen fiber deposits and an invasive tumor front. The findings have implications for the treatment of cancer stemness and for the prevention of tumor outgrowth through disseminated tumor cells.
Persistent Identifierhttp://hdl.handle.net/10722/295880
ISSN
2023 Impact Factor: 14.3
2023 SCImago Journal Rankings: 3.914
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNg, KY-
dc.contributor.authorShea, QT-
dc.contributor.authorWong, TL-
dc.contributor.authorLuk, ST-
dc.contributor.authorTong, M-
dc.contributor.authorLo, CM-
dc.contributor.authorMan, K-
dc.contributor.authorYun, JP-
dc.contributor.authorGuan, XY-
dc.contributor.authorLee, TK-
dc.contributor.authorZheng, YP-
dc.contributor.authorMa, S-
dc.date.accessioned2021-02-08T08:15:20Z-
dc.date.available2021-02-08T08:15:20Z-
dc.date.issued2021-
dc.identifier.citationAdvanced Science, 2021, v. 8 n. 5, article no. 2002483-
dc.identifier.issn2198-3844-
dc.identifier.urihttp://hdl.handle.net/10722/295880-
dc.description.abstractThe physical microenvironment is a critical mediator of tumor behavior. However, detailed biological and mechanistic insight is lacking. The present study reveals the role of chemotherapy-enriched CD133+ liver cancer stem cells (CSCs) with THBS2 deficiency. This subpopulation of cells contributes to a more aggressive cancer and functional stemness phenotype in hepatocellular carcinoma (HCC) by remodeling the extracellular matrix (ECM) through the regulation of matrix metalloproteinase (MMP) activity, collagen degradation, and matrix stiffness. The local soft spots created by these liver CSCs can enhance stemness and drug resistance and provide a route of escape to facilitate HCC metastasis. Interestingly, a positive feed-forward loop is identified where a local soft spot microenvironment in the HCC tumor is enriched with CD133 expressing cells that secrete markedly less ECM-modifying THBS2 upon histone H3 modification at its promoter region, allowing the maintenance of a localized soft spot matrix. Clinically, THBS2 deficiency is also correlated with low HCC survival, where high levels of CSCs with low THBS2 expression in HCC are associated with decreased collagen fiber deposits and an invasive tumor front. The findings have implications for the treatment of cancer stemness and for the prevention of tumor outgrowth through disseminated tumor cells.-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2198-3844-
dc.relation.ispartofAdvanced Science-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCancer stemness-
dc.subjectCD133-
dc.subjectHepatocellular carcinomas-
dc.subjectHistone modifications-
dc.subjectMatrix stiffness-
dc.subjectMechanoepigenetics-
dc.subjectMetastasis-
dc.subjectTHBS2-
dc.titleChemotherapy‐Enriched THBS2‐Deficient Cancer Stem Cells Drive Hepatocarcinogenesis through Matrix Softness Induced Histone H3 Modifications-
dc.typeArticle-
dc.identifier.emailNg, KY: jkyng@hku.hk-
dc.identifier.emailWong, TL: tinlwong@hku.hk-
dc.identifier.emailTong, M: caroltm@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hk-
dc.identifier.emailMa, S: stefma@hku.hk-
dc.identifier.authorityWong, TL=rp02845-
dc.identifier.authorityTong, M=rp02568-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityGuan, XY=rp00454-
dc.identifier.authorityMa, S=rp00506-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/advs.202002483-
dc.identifier.pmid33717837-
dc.identifier.pmcidPMC7927606-
dc.identifier.scopuseid_2-s2.0-85099049682-
dc.identifier.hkuros321073-
dc.identifier.volume8-
dc.identifier.issue5-
dc.identifier.spagearticle no. 2002483-
dc.identifier.epagearticle no. 2002483-
dc.identifier.isiWOS:000604282700001-
dc.publisher.placeGermany-

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