Teaming Up for Trouble: Cancer Cells, Transforming Growth Factor-β1 Signaling and the Epigenetic Corruption of Stromal Naïve Fibroblasts
Abstract
:1. Introduction
2. The Durable Gene Signature of Cancer-Associated Fibroblasts: Clonal Somatic Mutations or Epigenetic Changes?
3. Epigenetic Changes Underlie Trans-Differentiation of Stromal Fibroblasts to CAFs
3.1. Cancer-Associated Fibroblasts and the DNA Methylome
3.2. Cancer-Associated Fibroblasts and Post-Translational Histone Modifications
4. The Involvement of TGF-β1 Signaling in Shaping the Epigenetic Landscape of Cancer-Associated Fibroblasts
4.1. A Synopsis of TGF-β1 Signaling
4.2. TGF-β1 Signaling and the Epigenetic Signature of Cancer-Associated Fibroblasts
4.2.1. The ACTA2 Gene
4.2.2. The PLOD2 Gene
4.2.3. The COL1A1 Gene
4.2.4. The Thy1/CD90 Gene
4.2.5. The PTPN6 Gene
4.2.6. The Bet Proteins
4.2.7. The CAV-1 Gene
4.2.8. The VCAN Gene
4.2.9. TGF-β Signaling and Metabolic Reprogramming of Cancer-Associated Fibroblasts
5. TGF-β1 Signaling, Cancer-Associated Fibroblasts and Neoplasia: Colon Cancer as a Paradigm for the Human Disease
6. Concluding Remarks
7. Few (Out of Many) Outstanding Questions
Author Contributions
Conflicts of Interest
Abbreviations
CAFs | Cancer-associated fibroblasts |
TGF-β1 | Transforming Growth Factor-β1 |
CRC | Colorectal cancer |
TME | Tumor microenvironment |
EMT | Epithelial–mesenchymal transition |
ECM | Extracellular matrix |
LOH | Loss of heterozygosity |
FFPE | Formalin-fixed paraffin-embedded |
5mCyt | 5-methylcytosine |
DNMT | DNA methyl transferase |
NSCLC | Non-small cell lung cancer |
PDAC | Pancreatic ductal adenocarcinoma |
JAK | Janus kinase |
STAT | Signal transducer and activator of transcription protein |
SOCS1 | Suppressor of cytokine signaling 1 |
LIF | Leukemia-inducing factor |
LAP | Latency associated peptide |
LTBP | Large TGF-β binding protein |
SMAD | Suppressor of mothers against decapentaplegic |
SMURF | SMAD ubiquitin regulatory factor |
a-SMA | α-smooth muscle actin |
LHX | Lysyl hydroxylase |
HDAC | Histone deacetylase |
HAT | Histone acetyl transferase |
CMS | Colorectal cancer mesenchymal subtype |
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Lamprecht, S.; Sigal-Batikoff, I.; Shany, S.; Abu-Freha, N.; Ling, E.; Delinasios, G.J.; Moyal-Atias, K.; Delinasios, J.G.; Fich, A. Teaming Up for Trouble: Cancer Cells, Transforming Growth Factor-β1 Signaling and the Epigenetic Corruption of Stromal Naïve Fibroblasts. Cancers 2018, 10, 61. https://doi.org/10.3390/cancers10030061
Lamprecht S, Sigal-Batikoff I, Shany S, Abu-Freha N, Ling E, Delinasios GJ, Moyal-Atias K, Delinasios JG, Fich A. Teaming Up for Trouble: Cancer Cells, Transforming Growth Factor-β1 Signaling and the Epigenetic Corruption of Stromal Naïve Fibroblasts. Cancers. 2018; 10(3):61. https://doi.org/10.3390/cancers10030061
Chicago/Turabian StyleLamprecht, Sergio, Ina Sigal-Batikoff, Shraga Shany, Naim Abu-Freha, Eduard Ling, George J. Delinasios, Keren Moyal-Atias, John G. Delinasios, and Alexander Fich. 2018. "Teaming Up for Trouble: Cancer Cells, Transforming Growth Factor-β1 Signaling and the Epigenetic Corruption of Stromal Naïve Fibroblasts" Cancers 10, no. 3: 61. https://doi.org/10.3390/cancers10030061