Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13058-014-0429-3
Title: Trefoil factor 3 promotes metastatic seeding and predicts poor survival outcome of patients with mammary carcinoma
Authors: Pandey, V 
Wu, Z.-S
Zhang, M
Li, R
Zhang, J
Zhu, T
Lobie, P.E 
Keywords: estrogen receptor
messenger RNA
protein tyrosine kinase
STAT3 protein
trefoil factor 3 protein
trefoil peptide
unclassified drug
uvomorulin
cadherin
CDH1 protein, human
CSK tyrosine-protein kinase
peptide
protein tyrosine kinase
STAT3 protein
STAT3 protein, human
TFF3 protein, human
adult
animal experiment
animal model
animal tissue
Article
breast cancer cell line
breast carcinoma
cancer prognosis
cancer staging
cell adhesion
cell invasion
cell migration
colony formation
controlled study
down regulation
endothelium cell
gene expression
human
human cell
human tissue
lung metastasis
lymph node metastasis
major clinical study
marker gene
metastasis
mouse
nonhuman
oncogene
overall survival
protein expression
protein phosphorylation
recurrence free survival
tumor volume
animal
Bagg albino mouse
breast tumor
cancer transplantation
disease free survival
female
genetics
Kaplan Meier method
lung tumor
MCF 7 cell line
metabolism
middle aged
mortality
nude mouse
Paget nipple disease
pathology
phosphorylation
physiology
proportional hazards model
protein processing
secondary
tumor invasion
Animals
Breast Neoplasms
Cadherins
Carcinoma, Ductal, Breast
Disease-Free Survival
Female
Gene Expression
Humans
Kaplan-Meier Estimate
Lung Neoplasms
Lymphatic Metastasis
MCF-7 Cells
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Neoplasm Transplantation
Peptides
Phosphorylation
Proportional Hazards Models
Protein Processing, Post-Translational
src-Family Kinases
STAT3 Transcription Factor
Issue Date: 2014
Citation: Pandey, 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
Rights: Attribution 4.0 International
Abstract: Introduction: 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.
Source Title: Breast Cancer Research
URI: https://scholarbank.nus.edu.sg/handle/10635/183688
ISSN: 14655411
DOI: 10.1186/s13058-014-0429-3
Rights: Attribution 4.0 International
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