GREM1 signaling in cancer: tumor promotor and suppressor?
Journal
Journal of cell communication and signaling
ISSN: 1873-9601
Titre abrégé: J Cell Commun Signal
Pays: Netherlands
ID NLM: 101308338
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
20
01
2023
accepted:
07
06
2023
medline:
24
8
2023
pubmed:
24
8
2023
entrez:
24
8
2023
Statut:
ppublish
Résumé
GREMLIN1 (GREM1) is member of a family of structurally and functionally related secreted cysteine knot proteins, which act to sequester and inhibit the action of multifunctional bone morphogenetic proteins (BMPs). GREM1 binds directly to BMP dimers, thereby preventing BMP-mediated activation of BMP type I and type II receptors. Multiple reports identify the overexpression of GREM1 as a contributing factor in a broad range of cancers. Additionally, the GREM1 gene is amplified in a rare autosomal dominant inherited form of colorectal cancer. The inhibitory effects of GREM1 on BMP signaling have been linked to these tumor-promoting effects, including facilitating cancer cell stemness and the activation of cancer-associated fibroblasts. Moreover, GREM1 has been described to bind and signal to vascular endothelial growth factor receptor (VEGFR) and stimulate angiogenesis, as well as epidermal and fibroblast growth factor receptor (EGFR and FGFR) to elicit tumor-promoting effects in breast and prostate cancer, respectively. In contrast, a 2022 report revealed that GREM1 can promote an epithelial state in pancreatic cancers, thereby inhibiting pancreatic tumor growth and metastasis. In this commentary, we will review these disparate findings and attempt to provide clarity around the role of GREM1 signaling in cancer.
Identifiants
pubmed: 37615860
doi: 10.1007/s12079-023-00777-4
pii: 10.1007/s12079-023-00777-4
pmc: PMC10713512
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1517-1526Subventions
Organisme : Medical Research Council
ID : Medical Research Council
Pays : United Kingdom
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : National Centre for the Replacement, Refinement and Reduction of Animals in Research
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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