Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal
There exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/10164 |
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| author | David W. Freeman Elisa Rodrigues Sousa Sofia Karkampouna Eugenio Zoni Peter C. Gray David S. Salomon Marianna Kruithof-de Julio Benjamin T. Spike |
| author_facet | David W. Freeman Elisa Rodrigues Sousa Sofia Karkampouna Eugenio Zoni Peter C. Gray David S. Salomon Marianna Kruithof-de Julio Benjamin T. Spike |
| author_sort | David W. Freeman |
| collection | DOAJ |
| description | There exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more than a century, their clinical utility has yet to be fully realized1. This review highlights the small signaling protein CRIPTO encoded by the tumor derived growth factor 1 (<i>TDGF1</i>/<i>Tdgf1</i>) gene, an oft cited oncofetal protein whose presence in the cancer literature as a tumor promoter, diagnostic marker and viable therapeutic target continues to grow. We touch lightly on features well established and well-reviewed since its discovery more than 30 years ago, including CRIPTO’s early developmental roles and modulation of SMAD2/3 activation by a selected set of transforming growth factor β (TGF-β) family ligands. We predominantly focus instead on more recent and less well understood additions to the CRIPTO signaling repertoire, on its potential upstream regulators and on new conceptual ground for understanding its mode of action in the multicellular and often stressful contexts of neoplastic transformation and progression. We ask whence it re-emerges in cancer and where it ‘hides’ between the time of its fetal activity and its oncogenic reemergence. In this regard, we examine CRIPTO’s restriction to rare cells in the adult, its potential for paracrine crosstalk, and its emerging role in inflammation and tissue regeneration—roles it may reprise in tumorigenesis, acting on subsets of tumor cells to foster cancer initiation and progression. We also consider critical gaps in knowledge and resources that stand between the recent, exciting momentum in the CRIPTO field and highly actionable CRIPTO manipulation for cancer therapy and beyond. |
| first_indexed | 2024-03-10T07:35:08Z |
| format | Article |
| id | doaj.art-ad61ced48a4149ea8eec2eec8b96a271 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:08Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ad61ced48a4149ea8eec2eec8b96a2712023-11-22T13:33:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122181016410.3390/ijms221810164Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to HealDavid W. Freeman0Elisa Rodrigues Sousa1Sofia Karkampouna2Eugenio Zoni3Peter C. Gray4David S. Salomon5Marianna Kruithof-de Julio6Benjamin T. Spike7Department of Oncological Sciences, School of Medicine, University of Utah, Salt Lake City, UT 84113, USAUrology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3012 Bern, SwitzerlandUrology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3012 Bern, SwitzerlandUrology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3012 Bern, SwitzerlandPeptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USAMouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 20893, USAUrology Research Laboratory, Department for BioMedical Research DBMR, University of Bern, 3012 Bern, SwitzerlandDepartment of Oncological Sciences, School of Medicine, University of Utah, Salt Lake City, UT 84113, USAThere exists a set of factors termed oncofetal proteins that play key roles in ontogeny before they decline or disappear as the organism’s tissues achieve homeostasis, only to then re-emerge in cancer. Although the unique therapeutic potential presented by such factors has been recognized for more than a century, their clinical utility has yet to be fully realized1. This review highlights the small signaling protein CRIPTO encoded by the tumor derived growth factor 1 (<i>TDGF1</i>/<i>Tdgf1</i>) gene, an oft cited oncofetal protein whose presence in the cancer literature as a tumor promoter, diagnostic marker and viable therapeutic target continues to grow. We touch lightly on features well established and well-reviewed since its discovery more than 30 years ago, including CRIPTO’s early developmental roles and modulation of SMAD2/3 activation by a selected set of transforming growth factor β (TGF-β) family ligands. We predominantly focus instead on more recent and less well understood additions to the CRIPTO signaling repertoire, on its potential upstream regulators and on new conceptual ground for understanding its mode of action in the multicellular and often stressful contexts of neoplastic transformation and progression. We ask whence it re-emerges in cancer and where it ‘hides’ between the time of its fetal activity and its oncogenic reemergence. In this regard, we examine CRIPTO’s restriction to rare cells in the adult, its potential for paracrine crosstalk, and its emerging role in inflammation and tissue regeneration—roles it may reprise in tumorigenesis, acting on subsets of tumor cells to foster cancer initiation and progression. We also consider critical gaps in knowledge and resources that stand between the recent, exciting momentum in the CRIPTO field and highly actionable CRIPTO manipulation for cancer therapy and beyond.https://www.mdpi.com/1422-0067/22/18/10164CRIPTOstem cellsEMTcancermetastasisfibrosis |
| spellingShingle | David W. Freeman Elisa Rodrigues Sousa Sofia Karkampouna Eugenio Zoni Peter C. Gray David S. Salomon Marianna Kruithof-de Julio Benjamin T. Spike Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal International Journal of Molecular Sciences CRIPTO stem cells EMT cancer metastasis fibrosis |
| title | Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal |
| title_full | Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal |
| title_fullStr | Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal |
| title_full_unstemmed | Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal |
| title_short | Whence CRIPTO: The Reemergence of an Oncofetal Factor in ‘Wounds’ That Fail to Heal |
| title_sort | whence cripto the reemergence of an oncofetal factor in wounds that fail to heal |
| topic | CRIPTO stem cells EMT cancer metastasis fibrosis |
| url | https://www.mdpi.com/1422-0067/22/18/10164 |
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