Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal.

Freeman, David W; Rodrigues Sousa, Elisa; Karkampouna, Sofia; Zoni, Eugenio; Gray, Peter C; Salomon, David S; Kruithof-de Julio, Marianna; Spike, Benjamin T (2021). Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal. International journal of molecular sciences, 22(18) MDPI 10.3390/ijms221810164

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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 (TDGF1/Tdgf1) 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.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Rodrigues Sousa, Elisa; Zoni, Eugenio and Kruithof-de Julio, Marianna

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1422-0067

Publisher:

MDPI

Language:

English

Submitter:

Khiem Duong

Date Deposited:

12 Jan 2022 11:43

Last Modified:

12 Jan 2022 11:43

Publisher DOI:

10.3390/ijms221810164

PubMed ID:

34576327

Uncontrolled Keywords:

CRIPTO EMT cancer fibrosis metastasis stem cells therapeutic target

BORIS DOI:

10.48350/162239

URI:

https://boris.unibe.ch/id/eprint/162239

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