ArticleScientific reports2017
Targeting BMK1 Impairs the Drug Resistance to Combined Inhibition of BRAF and MEK1/2 in Melanoma.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- AXL is a novel ERK5/KLF4 target in MEK inhibitor-treated melanoma.Neoplasia (New York, N.Y.) · 2026Article
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy.Journal of medicinal chemistry · 2023Review
- The significance of ERK5 catalytic-independent functions in disease pathways.Frontiers in cell and developmental biology · 2023Review
- Immunomodulatory Properties of PI3K/AKT/mTOR and MAPK/MEK/ERK Inhibition Augment Response to Immune Checkpoint Blockade in Melanoma and Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Review
- The pleiotropic roles of circular and long noncoding RNAs in cutaneous melanoma.Molecular oncology · 2022Review
- ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled?Frontiers in cell and developmental biology · 2022Review
- ERK5 signalling pathway is a novel target of sorafenib: Implication in EGF biology.Journal of cellular and molecular medicine · 2021Article
- The MEK5/ERK5 Pathway in Health and Disease.International journal of molecular sciences · 2021Review
- Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.Biomolecules · 2021Review
- Playing the Whack-A-Mole Game: ERK5 Activation Emerges Among the Resistance Mechanisms to RAF-MEK1/2-ERK1/2- Targeted Therapy.Frontiers in cell and developmental biology · 2021Review
- Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for….Biochemical Society transactions · 2020Review
- Impact of ERK5 on the Hallmarks of Cancer.International journal of molecular sciences · 2019Review
- KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism.Cancer cell · 2018Article
- PML Recruits TET2 to Regulate DNA Modification and Cell Proliferation in Response to Chemotherapeutic Agent.Cancer research · 2018Article
- Article
- JNK, p38, ERK, and SGK1 Inhibitors in Cancer.Cancers · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to CIBM is inevitable and the drug resistance mechanisms still remain to be elucidated. Here, we show that BMK1 pathway contributes to the drug resistance to CIBM. Considering that ERK1/2 pathway regulates cellular processes by phosphorylating, we first performed a SILAC phosphoproteomic profiling of CIBM. Phosphorylation of 239 proteins was identified to be downregulated, while phosphorylation of 47 proteins was upregulated. Following siRNA screening of 47 upregulated proteins indicated that the knockdown of BMK1 showed the most significant ability to inhibit the proliferation of CIBM resistant cells. It was found that phosphorylation of BMK1 was enhanced in resistant cells, which suggested an association of BMK1 with drug resistance. Further study indicated that phospho-activation of BMK1 by MEK5D enhanced the resistance to CIBM. Conversely, inhibition of BMK1 by shRNAi or BMK1 inhibitor (XMD8-92) impaired not only the acquirement of resistance to CIBM, but also the proliferation of CIBM resistant cells. Further kinome-scale siRNA screening demonstrated that SRC\MEK5 cascade promotes the phospho-activation of BMK1 in response to CIBM. Our study not only provides a global phosphoproteomic view of CIBM in melanoma, but also demonstrates that inhibition of BMK1 has therapeutic potential for the treatment of melanoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.