Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.16950
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dc.titleTrefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent
dc.contributor.authorYou, M.-L
dc.contributor.authorChen, Y.-J
dc.contributor.authorChong, Q.-Y
dc.contributor.authorWu, M.-M
dc.contributor.authorPandey, V
dc.contributor.authorChen, R.-M
dc.contributor.authorLiu, L
dc.contributor.authorMa, L
dc.contributor.authorWu, Z.-S
dc.contributor.authorZhu, T
dc.contributor.authorLobie, P.E
dc.date.accessioned2020-09-01T00:58:33Z
dc.date.available2020-09-01T00:58:33Z
dc.date.issued2017
dc.identifier.citationYou, M.-L, Chen, Y.-J, Chong, Q.-Y, Wu, M.-M, Pandey, V, Chen, R.-M, Liu, L, Ma, L, Wu, Z.-S, Zhu, T, Lobie, P.E (2017). Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent. Oncotarget 8 (24) : 39323-39344. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.16950
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173805
dc.description.abstractThe efficacious treatment of hepatocellular carcinoma (HCC) remains a challenge, partially being attributed to intrinsic chemoresistance. Previous reports have observed increased TFF3 expression in HCC. Herein, we investigated the functional role of TFF3 in progression of HCC, and in both intrinsic and acquired chemoresistance. TFF3 expression was observed to be upregulated in HCC and associated with poor clinicopathological features and worse patient survival outcome. Functionally, forced expression of TFF3 in HCC cell lines increased cell proliferation, cell survival, anchorage-independent and 3D matrigel growth, cell invasion and migration, and in vivo tumor growth. In contrast, depleted expression of TFF3 decreased the oncogenicity of HCC cells as indicated by the above parameters. Furthermore, forced expression of TFF3 decreased doxorubicin sensitivity of HCC cells, which was attributed to increased doxorubicin efflux and cancer stem cell-like behavior of Hep3B cells. In contrast, depletion of TFF3 increased doxorubicin sensitivity and decreased cancer stem cell-like behavior of Hep3B cells. Correspondingly, TFF3 expression was markedly increased in Hep3B cells with acquired doxorubicin resistance, while the depletion of TFF3 resulted in re-sensitization of the Hep3B cells to doxorubicin. The increased doxorubicin efflux and enhanced cancer stem cell-like behavior of the doxorubicin-resistant Hep3B cells was observed to be dependent on TFF3 expression. In addition, we determined that TFF3-stimulated oncogenicity and chemoresistance in HCC cells was mediated by AKT-dependent expression of BCL-2. Hence, therapeutic inhibition of TFF3 should be considered to hinder HCC progression and overcome intrinsic and acquired chemoresistance in HCC. © You et al.
dc.sourceUnpaywall 20200831
dc.subjectdoxorubicin
dc.subjectprotein bcl 2
dc.subjectprotein kinase B
dc.subjecttrefoil factor 3
dc.subjectverapamil
dc.subjectanchorage independent growth
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectcancer growth
dc.subjectcancer resistance
dc.subjectcancer stem cell
dc.subjectcancer survival
dc.subjectcarcinogenicity
dc.subjectcell invasion
dc.subjectcell migration
dc.subjectcell proliferation
dc.subjectcell survival
dc.subjectclinical feature
dc.subjectcontrolled study
dc.subjectdrug targeting
dc.subjecthepatocellular carcinoma cell line
dc.subjecthistopathology
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectliver cell carcinoma
dc.subjectmajor clinical study
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprotein expression
dc.subjectprotein function
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.contributor.departmentDEPT OF CHEMISTRY
dc.description.doi10.18632/oncotarget.16950
dc.description.sourcetitleOncotarget
dc.description.volume8
dc.description.issue24
dc.description.page39323-39344
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