dc.contributor.author | Papageorgis, P. | en |
dc.contributor.author | Ozturk, S. | en |
dc.contributor.author | Lambert, A. W. | en |
dc.contributor.author | Neophytou, Christiana M. | en |
dc.contributor.author | Tzatsos, Alexandros | en |
dc.contributor.author | Wong, C. K. | en |
dc.contributor.author | Thiagalingam, S. | en |
dc.contributor.author | Constantinou, Andreas I. | en |
dc.creator | Papageorgis, P. | en |
dc.creator | Ozturk, S. | en |
dc.creator | Lambert, A. W. | en |
dc.creator | Neophytou, Christiana M. | en |
dc.creator | Tzatsos, Alexandros | en |
dc.creator | Wong, C. K. | en |
dc.creator | Thiagalingam, S. | en |
dc.creator | Constantinou, Andreas I. | en |
dc.date.accessioned | 2019-11-04T12:52:26Z | |
dc.date.available | 2019-11-04T12:52:26Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 1465-5411 | |
dc.identifier.uri | http://gnosis.library.ucy.ac.cy/handle/7/53285 | |
dc.description.abstract | Introduction: Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action. Methods: An unbiased approach using gene expression profiling of a BLBC progression model and in silico leveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was performed to assess its role in regulating breast cancer tumor growth and lung metastasis. Gene expression microarray analysis was followed by in vitro validation and cell migration assays to elucidate the downstream molecular pathways involved in this process. Results: We found that overexpression of the decoy receptor IL13Ralpha2 is significantly enriched in basal compared with luminal primary breast tumors as well as in a subset of metastatic basal-B breast cancer cells. Importantly, breast cancer patients with high-grade tumors and increased IL13Ralpha2 levels had significantly worse prognosis for metastasis-free survival compared with patients with low expression. Depletion of IL13Ralpha2 in metastatic breast cancer cells modestly delayed primary tumor growth but dramatically suppressed lung metastasis in vivo. Furthermore, IL13Ralpha2 silencing was associated with enhanced IL-13-mediated phosphorylation of signal transducer and activator of transcription 6 (STAT6) and impaired migratory ability of metastatic breast cancer cells. Interestingly, genome-wide transcriptional analysis revealed that IL13Ralpha2 knockdown and IL-13 treatment cooperatively upregulated the metastasis suppressor tumor protein 63 (TP63) in a STAT6-dependent manner. These observations are consistent with increased metastasis-free survival of breast cancer patients with high levels of TP63 and STAT6 expression and suggest that the STAT6-TP63 pathway could be involved in impairing metastatic dissemination of breast cancer cells to the lungs. Conclusion: Our findings indicate that IL13Ralpha2 could be used as a promising biomarker to predict patient outcome and provide a rationale for assessing the efficacy of anti-IL13Ralpha2 therapies in a subset of highly aggressive basal-like breast tumors as a strategy to prevent metastatic disease. © 2015 Papageorgis et al. | en |
dc.source | Breast Cancer Research | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84937911519&doi=10.1186%2fs13058-015-0607-y&partnerID=40&md5=440502228adb538b4e24d4e824b034b6 | |
dc.subject | human | en |
dc.subject | Humans | en |
dc.subject | Breast Neoplasms | en |
dc.subject | controlled study | en |
dc.subject | female | en |
dc.subject | prediction | en |
dc.subject | prognosis | en |
dc.subject | Disease-Free Survival | en |
dc.subject | disease free survival | en |
dc.subject | Lung Neoplasms | en |
dc.subject | metastasis | en |
dc.subject | Neoplasm Metastasis | en |
dc.subject | cancer prognosis | en |
dc.subject | protein expression | en |
dc.subject | Tumor Suppressor Proteins | en |
dc.subject | cancer grading | en |
dc.subject | procedures | en |
dc.subject | gene expression regulation | en |
dc.subject | nonhuman | en |
dc.subject | pathology | en |
dc.subject | signal transduction | en |
dc.subject | upregulation | en |
dc.subject | lung metastasis | en |
dc.subject | protein depletion | en |
dc.subject | Article | en |
dc.subject | lung tumor | en |
dc.subject | tumor marker | en |
dc.subject | human cell | en |
dc.subject | gene expression | en |
dc.subject | microarray analysis | en |
dc.subject | protein targeting | en |
dc.subject | animal cell | en |
dc.subject | animal experiment | en |
dc.subject | animal model | en |
dc.subject | animal tissue | en |
dc.subject | mouse | en |
dc.subject | gene expression profiling | en |
dc.subject | genetics | en |
dc.subject | genetic transcription | en |
dc.subject | transcriptome | en |
dc.subject | gene overexpression | en |
dc.subject | transcription factor | en |
dc.subject | Transcription Factors | en |
dc.subject | in vitro study | en |
dc.subject | cell migration | en |
dc.subject | gene silencing | en |
dc.subject | recurrence free survival | en |
dc.subject | secondary | en |
dc.subject | breast tumor | en |
dc.subject | tumor suppressor protein | en |
dc.subject | molecular mechanics | en |
dc.subject | gene identification | en |
dc.subject | interleukin 13 | en |
dc.subject | breast cancer cell line | en |
dc.subject | cancer inhibition | en |
dc.subject | phosphorylation | en |
dc.subject | computer model | en |
dc.subject | tumor cell line | en |
dc.subject | in vivo study | en |
dc.subject | STAT3 protein | en |
dc.subject | protein phosphorylation | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Lentivirinae | en |
dc.subject | Gene Expression Regulation, Neoplastic | en |
dc.subject | basal like breast cancer | en |
dc.subject | bioluminescence | en |
dc.subject | cell migration assay | en |
dc.subject | interleukin 13 receptor alpha2 | en |
dc.subject | Interleukin-13 Receptor alpha2 Subunit | en |
dc.subject | metastasis free survival | en |
dc.subject | metastasis inhibition | en |
dc.subject | protein p63 | en |
dc.subject | STAT6 protein | en |
dc.subject | STAT6 protein, human | en |
dc.subject | STAT6 Transcription Factor | en |
dc.subject | TP63 protein, human | en |
dc.title | Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis | en |
dc.type | info:eu-repo/semantics/article | |
dc.identifier.doi | 10.1186/s13058-015-0607-y | |
dc.description.volume | 17 | |
dc.author.faculty | Σχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences | |
dc.author.department | Τμήμα Βιολογικών Επιστημών / Department of Biological Sciences | |
dc.type.uhtype | Article | en |
dc.description.notes | <p>Cited By :9</p> | en |
dc.source.abbreviation | Breast Cancer Res. | en |
dc.contributor.orcid | Constantinou, Andreas I. [0000-0003-0365-1821] | |
dc.gnosis.orcid | 0000-0003-0365-1821 | |