التفاصيل البيبلوغرافية
| العنوان: |
Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung metastasis |
| المؤلفون: |
Papageorgis, Panagiotis, Ozturk, Sait, Lambert, Arthur W., Neophytou, Christiana M., Tzatsos, Alexandros, Wong, Chen K., Thiagalingam, Sam, Constantinou, Andreas I. |
| المصدر: |
Anatomy and Regenerative Biology Faculty Publications |
| بيانات النشر: |
Health Sciences Research Commons |
| سنة النشر: |
2015 |
| المجموعة: |
George Washington University: Health Sciences Research Commons (HSRC) |
| مصطلحات موضوعية: |
Breast Neoplasms--genetics, Interleukin-13 Receptor alpha2 Subunit--genetics, Lung Neoplasms--genetics, Neoplasm Metastasis--genetics, STAT6 Transcription Factor--genetics, Signal Transduction--genetics, Transcription Factors--genetics, Tumor Suppressor Proteins--genetics, Anatomy, Cancer Biology, Oncology |
| الوصف: |
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 silicoleveraging 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 ... |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
https://hsrc.himmelfarb.gwu.edu/smhs_anatregbio_facpubs/88Test; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/viewcontent/Targeting_IL13Ralpha2_activates_STAT6_TP63_pathway_to_suppress_breast_cancer_lung_metastasis.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/0/type/additional/viewcontent/Supplementary_materials_and_methods.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/1/type/additional/viewcontent/Figure_S1.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/2/type/additional/viewcontent/Figure_S2.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/3/type/additional/viewcontent/Figure_S3.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/4/type/additional/viewcontent/Figure_S4.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/5/type/additional/viewcontent/Figure_S5.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/6/type/additional/viewcontent/Figure_S6.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/7/type/additional/viewcontent/Figure_S7.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/8/type/additional/viewcontent/Figure_S8.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/9/type/additional/viewcontent/Figure_S9.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/10/type/additional/viewcontent/s13058_015_0607_y_s10.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/11/type/additional/viewcontent/Table_S1.pdfTest; https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/12/type/additional/viewcontent/Table_S2.pdfTest |
| DOI: |
10.1186/s13058-015-0607-y |
| الإتاحة: |
https://doi.org/10.1186/s13058-015-0607-yTest
https://hsrc.himmelfarb.gwu.edu/smhs_anatregbio_facpubs/88Test
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/viewcontent/Targeting_IL13Ralpha2_activates_STAT6_TP63_pathway_to_suppress_breast_cancer_lung_metastasis.pdfTest
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/0/type/additional/viewcontent/Supplementary_materials_and_methods.pdfTest
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/1/type/additional/viewcontent/Figure_S1.pdfTest
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/2/type/additional/viewcontent/Figure_S2.pdfTest
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/3/type/additional/viewcontent/Figure_S3.pdfTest
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/4/type/additional/viewcontent/Figure_S4.pdfTest
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/5/type/additional/viewcontent/Figure_S5.pdfTest
https://hsrc.himmelfarb.gwu.edu/context/smhs_anatregbio_facpubs/article/1087/filename/6/type/additional/viewcontent/Figure_S6.pdfTest |
| حقوق: |
http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.ECF801E3 |
| قاعدة البيانات: |
BASE |
