Targeting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in metastatic melanoma to increase efficacy of BRAFV600E inhibitors
TaeWon Kim
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Molecular and Environmental Toxicology Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Search for more papers by this authorThomas Havighurst
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Search for more papers by this authorKyungMann Kim
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Search for more papers by this authorMark Albertini
Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Medical Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin
Search for more papers by this authorCorresponding Author
Yaohui G. Xu
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Correspondence
Yaohui G. Xu, MD, PhD, Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 7th Floor, 1 South Park Street Madison 53715, WI.
Email: [email protected]
Vladimir S. Spiegelman, MD, PhD, Department of Pediatrics Division of Pediatric Hematology/Oncology Pennsylvania State University, College of Medicine Milton S. Hershey Medical Center PO Box 850, MC H085, C7830E 500 University Drive Hershey, 17033-0850 PA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Vladimir S. Spiegelman
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Department of Pediatrics, Pennsylvania State University, Hershey, Pennsylvania
Correspondence
Yaohui G. Xu, MD, PhD, Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 7th Floor, 1 South Park Street Madison 53715, WI.
Email: [email protected]
Vladimir S. Spiegelman, MD, PhD, Department of Pediatrics Division of Pediatric Hematology/Oncology Pennsylvania State University, College of Medicine Milton S. Hershey Medical Center PO Box 850, MC H085, C7830E 500 University Drive Hershey, 17033-0850 PA.
Email: [email protected]
Search for more papers by this authorTaeWon Kim
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Molecular and Environmental Toxicology Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Search for more papers by this authorThomas Havighurst
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Search for more papers by this authorKyungMann Kim
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Search for more papers by this authorMark Albertini
Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Medical Service, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin
Search for more papers by this authorCorresponding Author
Yaohui G. Xu
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Correspondence
Yaohui G. Xu, MD, PhD, Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 7th Floor, 1 South Park Street Madison 53715, WI.
Email: [email protected]
Vladimir S. Spiegelman, MD, PhD, Department of Pediatrics Division of Pediatric Hematology/Oncology Pennsylvania State University, College of Medicine Milton S. Hershey Medical Center PO Box 850, MC H085, C7830E 500 University Drive Hershey, 17033-0850 PA.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Vladimir S. Spiegelman
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
Department of Pediatrics, Pennsylvania State University, Hershey, Pennsylvania
Correspondence
Yaohui G. Xu, MD, PhD, Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 7th Floor, 1 South Park Street Madison 53715, WI.
Email: [email protected]
Vladimir S. Spiegelman, MD, PhD, Department of Pediatrics Division of Pediatric Hematology/Oncology Pennsylvania State University, College of Medicine Milton S. Hershey Medical Center PO Box 850, MC H085, C7830E 500 University Drive Hershey, 17033-0850 PA.
Email: [email protected]
Search for more papers by this authorAbstract
Melanoma is one of the deadliest forms of skin cancer. Although BRAF inhibitors significantly enhance survival of metastatic melanoma patients, most patients relapse after less than a year of treatment. We previously reported that mRNA binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is overexpressed in metastatic melanoma and that expression of IGF2BP1 confers resistance to chemotherapeutic agents. Here we demonstrate that IGF2BP1 plays an important role in the sensitivity of melanoma to targeted therapy. Inhibition of IGF2BP1 enhances the effects of BRAF-inhibitor and BRAF-MEK inhibitors in BRAFV600E melanoma. Also, knockdown of IGF2BP1 alone is sufficient to reduce tumorigenic characteristics in vemurafenib-resistant melanoma. These findings suggest that IGF2BP1 can be a novel therapeutic target for melanoma.
Supporting Information
Additional Supporting Information may be found online in the supporting information tab for this article.
| Filename | Description |
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| mc22786-sup-0001-SuppFig-S1.pdf337.4 KB |
Figure S1. Synergism of BRAF inhibition and IGF2BP1 knockdown. Figure S2. Reduced tumorigenic properties by vemurafenib and IGF2BP1 knockdown. Figure S3. Survival of vemurafenib-resistant cell lines at higher concentration of vemurafenib compared to parental cell lines. Figure S4. Reduced tumorigenic properties by inhibition of IGF2BP1 in resistant melanoma. Figure S5. Efficiency of IGF2BP1 knockdown using shIGF2BP1 in all cell lines used in this study. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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