دورية أكاديمية
BRAF Modulates Lipid Use and Accumulation.
| العنوان: | BRAF Modulates Lipid Use and Accumulation. |
|---|---|
| المؤلفون: | Turner JA; Division of Medical Oncology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA.; Medical Scientist Training Program, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA.; Department of Immunology and Microbiology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Paton EL; Division of Medical Oncology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Van Gulick R; Division of Medical Oncology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Stefanoni D; Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Cendali F; Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Reisz J; Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Tobin RP; Divion of Surgical Oncology, Department of Surgery, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., McCarter M; Divion of Surgical Oncology, Department of Surgery, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., D'Alessandro A; Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Torres RM; Department of Immunology and Microbiology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Robinson WA; Division of Medical Oncology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Couts KL; Division of Medical Oncology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA., Schlaepfer IR; Division of Medical Oncology, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USA. |
| المصدر: | Cancers [Cancers (Basel)] 2022 Apr 23; Vol. 14 (9). Date of Electronic Publication: 2022 Apr 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
| مستخلص: | There is increasing evidence that oxidative metabolism and fatty acids play an important role in BRAF-driven tumorigenesis, yet the effect of BRAF mutation and expression on metabolism is poorly understood. We examined how BRAF mutation and expression modulates metabolite abundance. Using the non-transformed NIH3T3 cell line, we generated cells that stably overexpressed BRAF V600E or BRAF WT. We found that cells expressing BRAF V600E were enriched with immunomodulatory lipids. Further, we found a unique transcriptional signature that was exclusive to BRAF V600E expression. We also report that BRAF V600E mutation promoted accumulation of long chain polyunsaturated fatty acids (PUFAs) and rewired metabolic flux for non-Warburg behavior. This cancer promoting mutation further induced the formation of tunneling nanotube (TNT)-like protrusions in NIH3T3 cells that preferentially accumulated lipid droplets. In the plasma of melanoma patients harboring the BRAF V600E mutation, levels of lysophosphatidic acid, sphingomyelin, and long chain fatty acids were significantly increased in the cohort of patients that did not respond to BRAF inhibitor therapy. Our findings show BRAF V600 status plays an important role in regulating immunomodulatory lipid profiles and lipid trafficking, which may inform future therapy across cancers. |
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| معلومات مُعتمدة: | R01 AI143261 United States AI NIAID NIH HHS; T32 GM007635 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: BRAF; lipids; melanoma; polyunsaturated |
| تواريخ الأحداث: | Date Created: 20220514 Latest Revision: 20221223 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9105200 |
| DOI: | 10.3390/cancers14092110 |
| PMID: | 35565240 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2072-6694 |
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| DOI: | 10.3390/cancers14092110 |