ANHB3323 Lecture Notes - Lecture 13: Fibroblast, Cellular Differentiation, Chemotherapy
3 Jun 2018
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LECTURE THIRTEEN: Cancer Epigenetics – from Mechanism to
Therapy
Epigenetics:
• Changes to DNA/associated proteins
• Alters gene expression without altering DNA sequence
• Histone modifications → methylation, acetylation, phosphorylation
• Not mutations → modifications
• Alterations are reversible
Epigenetic Processes:
• DNA methylation
• Histone post-transcriptional modifications
• Chromatin remodelers
• Non-coding RNA
• Any other agent that controls chromatin structure → nuclear architecture
Chromatin Remodeling:
• Organization of DNA-protein complexes (chromatin structure) different
between cell types
• Cancer cells → organization is more similar to stem cells/reprogrammed
cells
• Less chromatin packaging in cancer cells
• More OFF marks → less gene expression
DNA Methylation:
• Highly context dependent
• Methylation at CpG-rich promoters and first exons is associated with gene
repression
• DNA methylation is mitotically stable
• Can be dynamically and enzymatically remove in the cells →
erasure/resetting of epigenetic memory
Cancer Development:
• Multi step process
• Involves genetic and epigenetic alterations
• Leads to phenotypic plasticity
• Cancer progression
o Cells grow as benign tumor in epithelium
o Break through basal lamina
o Invade capillary → circulating tumor cells (CTCs)
o Adhere to blood vessel wall in another organ
o Escape from blood vessel (extravasation) → less than 1 in 1000
cells will survive
o Proliferate to form metastasis in another organ
• Metastasis dependent on epithelial to mesenchymal transition (EMT) and
mesenchymal to epithelial transition (MET)
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