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Cited by 8Melanoma and MAPK PathwaysProtein Degradation and InhibitorsChromatin Remodeling and Cancer

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

BRAFV600E dictates cell survival via c-Myc-dependent induction of Skp2 in human melanoma

Feng, Lin, Li, Jun, Bu, Xin, Zuo, Yan, Shen, Liangliang, Qu, Xuan·2020·Biochemical and Biophysical Research Communications
DOI 10.1016/j.bbrc.2019.12.085
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Abstract

BRAF V600E mutation is frequently observed in melanoma, and contributes to tumor malignancy. Despite inhibition of BRAF causes a profound cell growth inhibition and a strong clinical benefit in BRAF V600E melanoma, acquired drug resistance is still the major hurdle. In this study, we demonstrate that BRAF V600E drives cell growth and glycolysis in melanoma cells but does so by a previously unappreciated mechanism that involves direct induction of Skp2. Skp2 is highly expressed in melanoma tissues and particularly in tissues with BRAF V600E mutation. The inhibition of BRAF V600E by either siRNA or inhibitor vemurafenib suppressed Skp2 expression and cell growth. Mechanistic study shows that BRAF V600E suppression of Skp2 is dependent on c-Myc transcription factor via specifically bounding to the E-box region on SKP2 promoter. Further, the overexpression of Skp2 resulted in a markedly increase in cell growth, cell cycle progression and glycolysis which were repressed by BRAF V600E inhibition. Supporting the biological significance, Skp2 is specifically correlated with poor patient outcome in BRAF V600E but did not in BRAF WT melanomas. Thus, as a downstream target of BRAF V600E , Skp2 is critical for responses to BRAF inhibition, indicating targeting Skp2 might be a promising strategy for the treatment of BRAFi resistant melanomas.

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  • Upregulation of pioneer developmental organizers such as SOX2, KLF4, β-catenin, SNAIL-1, c-MYC, TBX3, and BCL6 is reported downstream of BRAF/MAPK-driven tumor.

    “Even upregulation of pioneer developmental organizers, such as SOX2, KLF4, β-catenin, SNAIL-1, c-MYC, TBX3, BCL6, et al., are reported downstream of BRAF/MAPK-driven tumor, the pathways causing lineage reprogramming are not clear12,15,30–36.”

    From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [31]

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Research works printed but not linked: 28

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Metadata

Authors
Feng, L., Li, J., Bu, X., Zuo, Y., Shen, L., & Qu, X.
Affiliations
  • Shaanxi University of Chinese Medicine (CN)
  • State Key Laboratory of Cancer Biology (CN)
  • Xizang Minzu University (CN)
Corresponding author
  • Shen, Liangliang
  • Qu, Xuan
ORCID
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2020-03
Volume
524
Issue
1
Pages
28-35
ISSN
0006-291X (ISSN-L)
DOI
10.1016/j.bbrc.2019.12.085
OpenAlex
W3002373991
Cited by
8
References
1
Citations by year
2025: 1 · 2024: 3 · 2022: 2 · 2021: 2
FWCI
0.32
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
BrafV600E, melanoma, Skp2, c-Myc, vemurafenib, BRAF inhibitor resistance, glycolysis, cell cycle progression, E-box promoter binding, cell survival, prognostic factors
MeSH terms
Vemurafenib, Cell Survival, Humans, Melanoma, Mutation, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc, Drug Resistance, Neoplasm, RNA, Small Interfering, S-Phase Kinase-Associated Proteins, Cell Line, Tumor, Protein Kinase Inhibitors, Proto-Oncogene Proteins B-raf, Cell Proliferation

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