Epigenetic control of cancer inflammation

Article Biology

MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming

Wazim Mohammed Ismail et al.

Summary: MacroH2A histone variants mark a subset of enhancers in normal and cancer cells, termed "macro-Bound Enhancers", which modulate enhancer activity. They are localized at enhancer elements lacking H3K27ac in a cell type-specific manner, maintaining cell identity. In breast cancer, reactivation of macro-bound enhancers is associated with oncogenic programs, while their repressive role is linked to macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Additionally, macroH2A deficiency enhances the activity of transcription factors associated with stem cell activity in normal mammary stem cells.

COMMUNICATIONS BIOLOGY (2023)

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Article Cell Biology

MacroH2A restricts inflammatory gene expression in melanoma cancer-associated fibroblasts by coordinating chromatin looping

Dan Filipescu et al.

Summary: Filipescu et al. demonstrate that MacroH2A deficiency in cancer-associated fibroblasts leads to altered chromatin looping and elevated inflammatory gene expression, resulting in impaired immune cell function and reduced anti-tumour response in melanoma. This study highlights the tumour suppressive role of MacroH2A variants in regulating chromatin architecture in the tumour stroma, with potential implications for human melanoma.

NATURE CELL BIOLOGY (2023)

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Review Oncology

Hallmarks of Cancer: New Dimensions

Douglas Hanahan

Summary: The concept of the hallmarks of cancer is a tool for simplifying the complexity of cancer phenotypes and genotypes into basic principles. This article proposes phenotypic plasticity and disrupted differentiation as distinct hallmark capabilities, and discusses nonmutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics. Additionally, the importance of senescent cells in the tumor microenvironment is highlighted. The integrative concept of the hallmarks of cancer helps in understanding the mechanisms of cancer development and applying that knowledge to cancer medicine.

CANCER DISCOVERY (2022)

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Article Cell Biology

MacroH2As regulate enhancer-promoter contacts affecting enhancer activity and sensitivity to inflammatory cytokines

David Corujo et al.

Summary: MacroH2A histone variants play a critical role in gene regulation, particularly in modulating the response of cancer cells to inflammatory signals. They affect the contact frequency between gene promoters and enhancers, and influence enhancer activity.

CELL REPORTS (2022)

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Article Oncology

The State of Melanoma: Emergent Challenges and Opportunities

Michael B. Atkins et al.

Summary: MRF conducted an assessment of challenges and opportunities in melanoma research community and patients five years ago, significant progress has been made since then. However, high incidence, recurrence, and death rates for melanoma remain. The Scientific Advisory Council and Breakthrough Consortium reconvened to discuss thematic areas essential to melanoma researchers and patients, helping to understand the challenges and opportunities facing the broader melanoma community today.

CLINICAL CANCER RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Profiling Cancer-Associated Fibroblasts in Melanoma

Federica Papaccio et al.

Summary: Research indicates that cancer-associated fibroblasts play significant roles in tumor growth, extracellular matrix remodeling, and inflammatory response. A thorough understanding of the melanoma-fibroblast relationship can expand treatment options.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Oncology

The Role of MacroH2A Histone Variants in Cancer

Chen-Jen Hsu et al.

Summary: This paper provides a concise review on a group of histone variants called macroH2A, discussing their additional domains that contribute to molecular functions in normal cells and their roles in gene expression and cancer. The importance of epigenetic regulation in physiological tissue homeostasis and malignant transformation is highlighted, with a focus on the least understood mechanism of histone variants. The study focuses on the tripartite structure of macroH2A histone variants and how they mediate molecular functions related to chromatin architecture, transcription, and DNA repair, emphasizing their dysregulated expression in different cancer subtypes and their variable prognostic impact.

CANCERS (2021)

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Article Cell Biology