Increased MARCKS Activity in BRAF Inhibitor-Resistant Melanoma Cells Is Essential for Their Enhanced Metastatic Behavior Independent of Elevated WNT5A and IL-6 Signaling
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Melanoma Cell Line Culture
2.2. Establishment of BRAFi-R Melanoma Cell Lines
2.3. MTT and WST1 Cell Proliferation Assays
2.4. Western Blotting
2.5. Migration and Invasion Assays
2.6. siRNA and shRNA Transfection
2.7. IL-6 ELISA and RhoA Activity Assay
2.8. Immunofluorescence Imaging
2.9. Evaluation of Tumor Cell Metastasis in a Zebrafish Model
2.10. Real-Time PCR
2.11. Statistical Analysis
3. Results
3.1. BRAFi-R Melanoma Cells Exhibit Enhanced MARCKS Expression and Phosphorylation of MARCKS at Serine-159 and Serine-163
3.2. Enhanced MARCKS Expression and Activity Are Independent of WNT5A and IL-6 in BRAFi-R Melanoma Cells
3.3. MARCKS Is an Attractive Antimetastatic Target in BRAFi-R Melanoma Cells
3.4. BRAFi-R Melanoma Cells Exhibit Enhanced PKC Isozyme and RhoA Activities
3.5. Endogenous Basal PKC Activity and RhoA Activity Independently Contribute to MARCKS Activation in BRAFi-R Melanoma Cells
4. Discussion
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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Yadav, V.; Jobe, N.; Satapathy, S.R.; Mohapatra, P.; Andersson, T. Increased MARCKS Activity in BRAF Inhibitor-Resistant Melanoma Cells Is Essential for Their Enhanced Metastatic Behavior Independent of Elevated WNT5A and IL-6 Signaling. Cancers 2022, 14, 6077. https://doi.org/10.3390/cancers14246077
Yadav V, Jobe N, Satapathy SR, Mohapatra P, Andersson T. Increased MARCKS Activity in BRAF Inhibitor-Resistant Melanoma Cells Is Essential for Their Enhanced Metastatic Behavior Independent of Elevated WNT5A and IL-6 Signaling. Cancers. 2022; 14(24):6077. https://doi.org/10.3390/cancers14246077
Chicago/Turabian StyleYadav, Vikas, Njainday Jobe, Shakti Ranjan Satapathy, Purusottam Mohapatra, and Tommy Andersson. 2022. "Increased MARCKS Activity in BRAF Inhibitor-Resistant Melanoma Cells Is Essential for Their Enhanced Metastatic Behavior Independent of Elevated WNT5A and IL-6 Signaling" Cancers 14, no. 24: 6077. https://doi.org/10.3390/cancers14246077