Shifting the Focus of Signaling Abnormalities in Colon Cancer
Colon cancer tumorigenesis occurs incrementally. The process involves the acquisition of mutations which typically follow an established pattern: activation of WNT signaling, activation of RAS signaling, and inhibition of TGF-β signaling. This arrangement recapitulates, to some degree, the stem cell...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/3/784 |
| _version_ | 1797488640450887680 |
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| author | Markus A. Brown Thomas Ried |
| author_facet | Markus A. Brown Thomas Ried |
| author_sort | Markus A. Brown |
| collection | DOAJ |
| description | Colon cancer tumorigenesis occurs incrementally. The process involves the acquisition of mutations which typically follow an established pattern: activation of WNT signaling, activation of RAS signaling, and inhibition of TGF-β signaling. This arrangement recapitulates, to some degree, the stem cell niche of the intestinal epithelium, which maintains WNT and EGF activity while suppressing TGF-β. The resemblance between the intestinal stem cell environment and colon cancer suggests that the concerted activity of these pathways generates and maintains a potent growth-inducing stimulus. However, each pathway has a myriad of downstream targets, making it difficult to identify which aspects of these pathways are drivers. To address this, we utilize the cell cycle, the ultimate regulator of cell proliferation, as a foundation for cross-pathway integration. We attempt to generate an overview of colon cancer signaling patterns by integrating the major colon cancer signaling pathways in the context of cell replication, specifically, the entrance from G<sub>1</sub> into S-phase. |
| first_indexed | 2024-03-10T00:05:12Z |
| format | Article |
| id | doaj.art-523b53d650b5481d969fa8ac293123ec |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:05:12Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-523b53d650b5481d969fa8ac293123ec2023-11-23T16:08:36ZengMDPI AGCancers2072-66942022-02-0114378410.3390/cancers14030784Shifting the Focus of Signaling Abnormalities in Colon CancerMarkus A. Brown0Thomas Ried1Genetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USAGenetics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USAColon cancer tumorigenesis occurs incrementally. The process involves the acquisition of mutations which typically follow an established pattern: activation of WNT signaling, activation of RAS signaling, and inhibition of TGF-β signaling. This arrangement recapitulates, to some degree, the stem cell niche of the intestinal epithelium, which maintains WNT and EGF activity while suppressing TGF-β. The resemblance between the intestinal stem cell environment and colon cancer suggests that the concerted activity of these pathways generates and maintains a potent growth-inducing stimulus. However, each pathway has a myriad of downstream targets, making it difficult to identify which aspects of these pathways are drivers. To address this, we utilize the cell cycle, the ultimate regulator of cell proliferation, as a foundation for cross-pathway integration. We attempt to generate an overview of colon cancer signaling patterns by integrating the major colon cancer signaling pathways in the context of cell replication, specifically, the entrance from G<sub>1</sub> into S-phase.https://www.mdpi.com/2072-6694/14/3/784WNT signalingRAS signalingTGF-β signalingβ-cateninK-RASSMAD4 |
| spellingShingle | Markus A. Brown Thomas Ried Shifting the Focus of Signaling Abnormalities in Colon Cancer Cancers WNT signaling RAS signaling TGF-β signaling β-catenin K-RAS SMAD4 |
| title | Shifting the Focus of Signaling Abnormalities in Colon Cancer |
| title_full | Shifting the Focus of Signaling Abnormalities in Colon Cancer |
| title_fullStr | Shifting the Focus of Signaling Abnormalities in Colon Cancer |
| title_full_unstemmed | Shifting the Focus of Signaling Abnormalities in Colon Cancer |
| title_short | Shifting the Focus of Signaling Abnormalities in Colon Cancer |
| title_sort | shifting the focus of signaling abnormalities in colon cancer |
| topic | WNT signaling RAS signaling TGF-β signaling β-catenin K-RAS SMAD4 |
| url | https://www.mdpi.com/2072-6694/14/3/784 |
| work_keys_str_mv | AT markusabrown shiftingthefocusofsignalingabnormalitiesincoloncancer AT thomasried shiftingthefocusofsignalingabnormalitiesincoloncancer |