Autocrine TGFβ1 Opposes Exogenous TGFβ1-Induced Cell Migration and Growth Arrest through Sustainment of a Feed-Forward Loop Involving MEK-ERK Signaling
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Divergent Effects of Endogenous and Exogenous TGFβ1 on TGFβ Target Genes
2.2. Knockdown of TGFB1 Enhances the Migratory Response to rhTGFβ1
2.3. Ectopic TGFB1 Antagonizes Basal and rhTGFβ1-Induced Migration in MDA-MB-231 Cells but Synergizes with rhTGFβ1-Induced Migration in Panc1 Cells
2.4. Endogenous TGFB1 Opposes rhTGFβ1-Induced Growth Arrest and Induction of p21WAF1 Expression
2.5. Mutual Induction of aTGFβ1 or ERK Activation Sustains Proliferation
2.6. Effect of Inhibition of the ALK5 Kinase on TGFB1 Expression, Cell Migration, and ERK2 Activation
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Treatments
4.2. Transient Transfections
4.3. Quantitative Real-Time PCR Analysis
4.4. Western Blotting
4.5. TGFβ1 ELISA
4.6. (3H)-Thymidine Incorporation Assay
4.7. Real-Time Cell Migration Assays
4.8. Proliferation Assays
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ungefroren, H.; Christl, J.; Eiden, C.; Wellner, U.F.; Lehnert, H.; Marquardt, J.-U. Autocrine TGFβ1 Opposes Exogenous TGFβ1-Induced Cell Migration and Growth Arrest through Sustainment of a Feed-Forward Loop Involving MEK-ERK Signaling. Cancers 2021, 13, 1357. https://doi.org/10.3390/cancers13061357
Ungefroren H, Christl J, Eiden C, Wellner UF, Lehnert H, Marquardt J-U. Autocrine TGFβ1 Opposes Exogenous TGFβ1-Induced Cell Migration and Growth Arrest through Sustainment of a Feed-Forward Loop Involving MEK-ERK Signaling. Cancers. 2021; 13(6):1357. https://doi.org/10.3390/cancers13061357
Chicago/Turabian StyleUngefroren, Hendrik, Jessica Christl, Caroline Eiden, Ulrich F. Wellner, Hendrik Lehnert, and Jens-Uwe Marquardt. 2021. "Autocrine TGFβ1 Opposes Exogenous TGFβ1-Induced Cell Migration and Growth Arrest through Sustainment of a Feed-Forward Loop Involving MEK-ERK Signaling" Cancers 13, no. 6: 1357. https://doi.org/10.3390/cancers13061357