Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13058-014-0429-3
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dc.titleTrefoil factor 3 promotes metastatic seeding and predicts poor survival outcome of patients with mammary carcinoma
dc.contributor.authorPandey, V
dc.contributor.authorWu, Z.-S
dc.contributor.authorZhang, M
dc.contributor.authorLi, R
dc.contributor.authorZhang, J
dc.contributor.authorZhu, T
dc.contributor.authorLobie, P.E
dc.date.accessioned2020-11-19T07:14:02Z
dc.date.available2020-11-19T07:14:02Z
dc.date.issued2014
dc.identifier.citationPandey, V, Wu, Z.-S, Zhang, M, Li, R, Zhang, J, Zhu, T, Lobie, P.E (2014). Trefoil factor 3 promotes metastatic seeding and predicts poor survival outcome of patients with mammary carcinoma. Breast Cancer Research 16 (1) : 429. ScholarBank@NUS Repository. https://doi.org/10.1186/s13058-014-0429-3
dc.identifier.issn14655411
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/183688
dc.description.abstractIntroduction: Recurrence or early metastasis remains the predominant cause of mortality in patients with estrogen receptor positive (ER+) mammary carcinoma (MC). However, the molecular mechanisms underlying the initial progression of ER+ MC to metastasis remains poorly understood. Trefoil factor 3 (TFF3) is an estrogen-responsive oncogene in MC. Herein, we provide evidence for a functional role of TFF3 in metastatic progression of ER+ MC. Methods: The association of TFF3 expression with clinicopathological parameters and survival outcome in a cohort of MC patients was assessed by immunohistochemistry. The expression of TFF3 in MCF7 and T47D cells was modulated by forced expression or siRNA-mediated depletion of TFF3. mRNA and protein levels were determined using qPCR and western blot. The functional effect of modulation of TFF3 expression in MC cells was determined in vitro and in vivo. Mechanistic analyses were performed using reporter constructs, modulation of signal transducer and activator of transcription 3 (STAT3) expression, and pharmacological inhibitors against c-SRC and STAT3 activity. Results: TFF3 protein expression was positively associated with larger tumour size, lymph node metastasis, higher stage, and poor survival outcome. Forced expression of TFF3 in ER+ MC cells stimulated colony scattering, cell adhesion to a Collagen I-coated matrix, colony formation on a Collagen I- or Matrigel-coated matrix, endothelial cell adhesion, and transmigration through an endothelial cell barrier. In vivo, forced expression of TFF3 in MCF7 cells stimulated the formation of metastatic nodules in animal lungs. TFF3 regulation of the mRNA levels of epithelial, mesenchymal, and metastatic-related genes in ER+ MC cells were consistent with the altered cell behaviour. Forced expression of TFF3 in ER+ MC cells stimulated phosphorylation of c-SRC that subsequently increased STAT3 activity, which lead to the downregulation of E-cadherin. siRNA-mediated depletion of TFF3 reduced the invasiveness of ER+ MC cells. Conclusions: TFF3 expression predicts metastasis and poor survival outcome of patients with MC and functionally stimulates cellular invasion and metastasis of ER+ MC cells. Adjuvant functional inhibition of TFF3 may therefore be considered to ameliorate outcome of ER+ MC patients. © 2014 Pandey et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectestrogen receptor
dc.subjectmessenger RNA
dc.subjectprotein tyrosine kinase
dc.subjectSTAT3 protein
dc.subjecttrefoil factor 3 protein
dc.subjecttrefoil peptide
dc.subjectunclassified drug
dc.subjectuvomorulin
dc.subjectcadherin
dc.subjectCDH1 protein, human
dc.subjectCSK tyrosine-protein kinase
dc.subjectpeptide
dc.subjectprotein tyrosine kinase
dc.subjectSTAT3 protein
dc.subjectSTAT3 protein, human
dc.subjectTFF3 protein, human
dc.subjectadult
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbreast cancer cell line
dc.subjectbreast carcinoma
dc.subjectcancer prognosis
dc.subjectcancer staging
dc.subjectcell adhesion
dc.subjectcell invasion
dc.subjectcell migration
dc.subjectcolony formation
dc.subjectcontrolled study
dc.subjectdown regulation
dc.subjectendothelium cell
dc.subjectgene expression
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectlung metastasis
dc.subjectlymph node metastasis
dc.subjectmajor clinical study
dc.subjectmarker gene
dc.subjectmetastasis
dc.subjectmouse
dc.subjectnonhuman
dc.subjectoncogene
dc.subjectoverall survival
dc.subjectprotein expression
dc.subjectprotein phosphorylation
dc.subjectrecurrence free survival
dc.subjecttumor volume
dc.subjectanimal
dc.subjectBagg albino mouse
dc.subjectbreast tumor
dc.subjectcancer transplantation
dc.subjectdisease free survival
dc.subjectfemale
dc.subjectgenetics
dc.subjectKaplan Meier method
dc.subjectlung tumor
dc.subjectMCF 7 cell line
dc.subjectmetabolism
dc.subjectmiddle aged
dc.subjectmortality
dc.subjectnude mouse
dc.subjectPaget nipple disease
dc.subjectpathology
dc.subjectphosphorylation
dc.subjectphysiology
dc.subjectproportional hazards model
dc.subjectprotein processing
dc.subjectsecondary
dc.subjecttumor invasion
dc.subjectAnimals
dc.subjectBreast Neoplasms
dc.subjectCadherins
dc.subjectCarcinoma, Ductal, Breast
dc.subjectDisease-Free Survival
dc.subjectFemale
dc.subjectGene Expression
dc.subjectHumans
dc.subjectKaplan-Meier Estimate
dc.subjectLung Neoplasms
dc.subjectLymphatic Metastasis
dc.subjectMCF-7 Cells
dc.subjectMice, Inbred BALB C
dc.subjectMice, Nude
dc.subjectMiddle Aged
dc.subjectNeoplasm Invasiveness
dc.subjectNeoplasm Transplantation
dc.subjectPeptides
dc.subjectPhosphorylation
dc.subjectProportional Hazards Models
dc.subjectProtein Processing, Post-Translational
dc.subjectsrc-Family Kinases
dc.subjectSTAT3 Transcription Factor
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.description.doi10.1186/s13058-014-0429-3
dc.description.sourcetitleBreast Cancer Research
dc.description.volume16
dc.description.issue1
dc.description.page429
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