Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells
Abstract
:1. Introduction
2. Results
2.1. Differential Regulation of Low-Density Lipoprotein Receptor (LDLR) Protein Expression and Low-Density Lipoprotein (LDL) Uptake in Papillary Thyroid Carcinoma (PTC) Cell Lines with Different Mutational Status after LDL Incubation
2.2. LDL Promotes Higher Proliferation Levels and Decreases Adhesion Capacity in the BCPAP Cell Line, in Comparison to the Constant Proliferation and Cellular Migration Promoted by LDL in the TPC1 Cell Line
2.3. LDL Enhances the RAS/RAF/MAPK (MEK)/ERK Pathway
2.4. Vemurafenib Reduces Cellular Proliferation Promoted by LDL, Downregulating LDLR Expression and Impairing RAS/RAF/MAPK (MEK)/ERK Pathway Activation in BCPAP Cell Line
2.5. LDLR Is Required for LDL-Mediated Induction of RAS/RAF/MAPK (MEK)/ERK Pathway, LDL-Uptake and Cell Proliferation in the BCPAP Cell Line
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Cell Culture
4.2. Human LDL Isolation
4.3. Labeling LDL with DiI
4.4. Analysis of Lipoprotein Uptake by a Fluorometric Assay
4.5. Analysis of Lipoprotein Uptake by Confocal Microscopy
4.6. Quantitative Real-Time PCR
4.7. Protein Extraction and Western Blot
4.8. MTT Assay
4.9. Migration and Adhesion Assay
4.10. Transient Transfection Assay
4.11. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Revilla, G.; Ruiz-Auladell, L.; Vallverdú, N.F.; Santamaría, P.; Moral, A.; Pérez, J.I.; Li, C.; Fuste, V.; Lerma, E.; Corcoy, R.; et al. Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells. Int. J. Mol. Sci. 2023, 24, 11153. https://doi.org/10.3390/ijms241311153
Revilla G, Ruiz-Auladell L, Vallverdú NF, Santamaría P, Moral A, Pérez JI, Li C, Fuste V, Lerma E, Corcoy R, et al. Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells. International Journal of Molecular Sciences. 2023; 24(13):11153. https://doi.org/10.3390/ijms241311153
Chicago/Turabian StyleRevilla, Giovanna, Lara Ruiz-Auladell, Núria Fucui Vallverdú, Paula Santamaría, Antonio Moral, José Ignacio Pérez, Changda Li, Victoria Fuste, Enrique Lerma, Rosa Corcoy, and et al. 2023. "Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells" International Journal of Molecular Sciences 24, no. 13: 11153. https://doi.org/10.3390/ijms241311153