Adipocyte-Derived Leptin Promotes PAI-1-Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture and Reagents
2.2. Coculture, Conditioned Medium Collection and Migration Assays
2.3. Wound Healing Scratch Assays and 3D Invasion Assays
2.4. Cytokine Protein Arrays
2.5. Transfection and Generation of Stable Cells
2.6. Transient Transfection with siRNA or miR-34a Mimic
2.7. Recombinant Human Leptin
2.8. In Vivo Studies
2.9. RNA Isolation and qRT-PCR
2.10. Proteins Extraction and Western Blot Analysis
2.11. Immunofluorescence and Immunohistochemistry Assay
2.12. Databases
2.13. Statistical Analysis
3. Results
3.1. Adipocytes Potentiate Breast Cancer Metastasis by Upregulating PAI-1
3.2. PAI-1 Induces EMT and the Metastatic Properties of Breast Cancer Cells
3.3. Adipocyte-Derived Leptin Facilitates PAI-1-Mediated Breast Cancer Metastasis
3.4. Repression of MiR-34a Contributes to Leptin/OBR-Induced PAI-1 Expression
3.5. STAT3 Mediates the Leptin/OBR Induced Repression of miR-34a and Activation of PAI-1
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Ethics Approval and Consent to Participate
Abbreviations
TME | Tumor microenvironment |
CAFs | Cancer-associated fibroblasts |
TAMs | Tumor-associated macrophage |
ASCs | Adipose stem cells |
CAAs | Cancer-associated adipocytes |
ECM | Extracellular matrix |
CHAT | Cancer Hallmarks Analytics Tool |
CM | Conditioned medium |
ILC | Invasive lobular breast carcinom |
IDC | Invasive ductal breast carcinoma |
MLD | Mixed lobular & ductal breast carcinoma |
PAI-1/SERPINE1 | Plasminogen activator inhibitor 1 |
OBR/LEPR | Leptin receptor |
IF | Immunofluorescence |
IHC | Immunohistochemistry |
WB | Western blot |
OS | Overall survival |
DMFS | Distance metastasis free survival |
PS | Postsurgical survival |
RFS | Relapse free survival |
EMT | Epithelial-mesenchymal transition |
F-actin | Filamentous actin |
TNBC | Triple negative breast cancer |
TFs | Transcription factors |
OXPHOS | Oxidative phosphorylation |
miRNAs | MicroRNAs |
NSCLC | Non-small-cell lung cancer |
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Li, S.-J.; Wei, X.-H.; Zhan, X.-M.; He, J.-Y.; Zeng, Y.-Q.; Tian, X.-M.; Yuan, S.-T.; Sun, L. Adipocyte-Derived Leptin Promotes PAI-1-Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner. Cancers 2020, 12, 3864. https://doi.org/10.3390/cancers12123864
Li S-J, Wei X-H, Zhan X-M, He J-Y, Zeng Y-Q, Tian X-M, Yuan S-T, Sun L. Adipocyte-Derived Leptin Promotes PAI-1-Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner. Cancers. 2020; 12(12):3864. https://doi.org/10.3390/cancers12123864
Chicago/Turabian StyleLi, Si-Jing, Xiao-Hui Wei, Xiao-Man Zhan, Jin-Yong He, Yu-Qi Zeng, Xue-Mei Tian, Sheng-Tao Yuan, and Li Sun. 2020. "Adipocyte-Derived Leptin Promotes PAI-1-Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner" Cancers 12, no. 12: 3864. https://doi.org/10.3390/cancers12123864
APA StyleLi, S.-J., Wei, X.-H., Zhan, X.-M., He, J.-Y., Zeng, Y.-Q., Tian, X.-M., Yuan, S.-T., & Sun, L. (2020). Adipocyte-Derived Leptin Promotes PAI-1-Mediated Breast Cancer Metastasis in a STAT3/miR-34a Dependent Manner. Cancers, 12(12), 3864. https://doi.org/10.3390/cancers12123864