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: 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.
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Authors | Panagiotis Papageorgis, Sait Ozturk, Arthur W Lambert, Christiana M Neophytou, Alexandros Tzatsos, Chen K Wong, Sam Thiagalingam, Andreas I Constantinou |
Journal | Breast cancer research : BCR
(Breast Cancer Res)
Vol. 17
Pg. 98
(Jul 25 2015)
ISSN: 1465-542X [Electronic] England |
PMID | 26208975
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interleukin-13 Receptor alpha2 Subunit
- STAT6 Transcription Factor
- STAT6 protein, human
- TP63 protein, human
- Transcription Factors
- Tumor Suppressor Proteins
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Topics |
- Breast Neoplasms
(genetics, pathology)
- Cell Line, Tumor
- Disease-Free Survival
- Female
- Gene Expression Profiling
(methods)
- Gene Expression Regulation, Neoplastic
(genetics)
- Humans
- Interleukin-13 Receptor alpha2 Subunit
(genetics)
- Lung Neoplasms
(genetics, pathology, secondary)
- Neoplasm Metastasis
(genetics, pathology)
- Phosphorylation
(genetics)
- Prognosis
- STAT6 Transcription Factor
(genetics)
- Signal Transduction
(genetics)
- Transcription Factors
(genetics)
- Tumor Suppressor Proteins
(genetics)
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