AI Article Synopsis
- The study investigates the relationship between Mcl-1, a protein important for melanoma cell survival, and oncogenic BRAF signaling, particularly focusing on how BRAF mutations affect Mcl-1 expression in melanoma cell lines.
- Findings reveal that BRAF(V600E) mutant melanoma cells exhibit increased expression of Mcl-1L and Mcl-1S compared to normal skin cells and primary melanocytes, indicating a potential link between BRAF activation and Mcl-1 levels.
- The research suggests that targeting the overexpression of Mcl-1 caused by BRAF mutations could help counteract melanoma's resistance to apoptosis, presenting a potential therapeutic approach using Mcl-1 inhibitors.
Article Abstract
The Bcl-2 family member Mcl-1 is essential for melanoma survival; however, the influence of oncogenic BRAF signalling remains elusive. In this study, Mcl-1 splice variant expression was determined in a panel of melanoma cell lines in relation to BRAF mutational status. Mcl-1L mRNA expression was increased in melanoma cells compared with primary melanocytes with significantly increased mRNA and protein expression observed in BRAF(V600E) mutant melanoma cells. Although no change in Mcl-1S mRNA was observed, Mcl-1S protein expression also increased in BRAF mutant melanoma cells. Additionally, while over-expression of mutant BRAF(V600E) increased both Mcl-1L and Mcl-1S expression, inhibition of hyperactive BRAF signalling resulted in decreased Mcl-1L expression. These studies suggest that the regulation of Mcl-1 expression by BRAF signalling is increased by oncogenic activation of BRAF, revealing a mechanism of apoptotic resistance which may be overcome by the use of more specifically targeted Mcl-1 inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/exd.12254 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigating the biomarker potential and molecular targets of TIGD1 in lung cancer using bioinformatics.
Turk J Med Sci
December 2024
Department of Medical Biology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkiye.
Background/aim: Lung cancer, a predominant contributor to cancer mortality, is characterized by diverse etiological factors, including tobacco smoking and genetic susceptibilities. Despite advancements, particularly in nonsmall-cell lung cancer (NSCLC), therapeutic options for lung squamous cell carcinoma (LUSC) are limited. Transposable elements (TEs) and their regulatory proteins, such as tigger transposable element derived (TIGD) family proteins, have been implicated in cancer development.
View Article and Find Full Text PDFBraf-Mutant Melanomas: Biology and Therapy.
Curr Oncol
December 2024
Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
The incidence of melanoma, the most lethal form of skin cancer, has increased mainly due to ultraviolet exposure. The molecular characterization of melanomas has shown a high mutational burden led to the identification of some recurrent genetic alterations. gene is mutated in 40-50% of melanomas and its role in melanoma development is paramount.
View Article and Find Full Text PDFEfficacy of Combined Encorafenib and Binimetinib Treatment for Erdheim-Chester Disease Harboring Concurrent BRAF and KRAS Mutations: A Case Report.
Cancer Rep (Hoboken)
December 2024
Department of Hematology and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Background: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with diverse clinical manifestations, often associated with mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. BRAF and KRAS mutations, which are driver mutations of oncogenes, participate in the same signaling pathway (MAPK/ERK pathway) and are usually mutually exclusive. We report a case of ECD with concurrent BRAF and KRAS mutations treated using BRAF and MEK inhibitors.
View Article and Find Full Text PDFDeciphering TGF-β1's Role in Drug Resistance and Leveraging Plant Bioactives for Cancer Therapy.
Eur J Pharmacol
December 2024
School of Health Sciences and Technology, UPES, Dehradun, Uttarakhand, 248007, India. Electronic address:
The intricate regulatory mechanisms governing TGF-β1 expression play pivotal roles in tumor progression. Key proteins such as FKBP1A, SMAD6, and SMAD7 trigger this process, modulating cell growth inhibition via p15INK4b and p21CIP1 induction. Despite TGF-β's tumor-suppressive functions, cancer cells adeptly evade its effects, fueling disease advancement.
View Article and Find Full Text PDFRAS is a common driver of cancer that was considered undruggable for decades. Recent advances have enabled the development of RAS inhibitors, but the efficacy of these inhibitors remains limited by resistance. Here, we developed a pan-RAS inhibitor, ADT-007, that binds nucleotide-free RAS to block GTP activation of effector interactions and MAPK/AKT signaling, resulting in mitotic arrest and apoptosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!