- |||||||||| CRIPTO-regulated extracellular vesicles mediate heterotypic cellular crosstalk in triple negative breast cancers (Section 13) - Mar 5, 2024 - Abstract #AACR2024AACR_9547;
We find that inhibition of CRIPTO with A4Fc suppresses cancer associated fibroblast (CAF) activation and collagen remodeling in vivo. Further, by modeling tumor cell:fibroblast crosstalk in vitro, we have demonstrated mechanistically that CRIPTO expression in tumor cells mediates subsequent extracellular vesicle (EV) uptake by fibroblasts, as well as fibroblast SMAD pathway activation and priming for reciprocal signaling back to tumor cells to promote transcriptional reprogramming and cellular invasion.The significance of these findings lies in their elucidation of key EV control mechanisms that could be exploited to intervene in essential tumor cell:fibroblast crosstalk or to enhance targeting of therapeutic moieties based on EV architecture and function in cancer and/or normative regenerative processes.
- |||||||||| thapsigargin / University of Nottingham, Pirbright Institute
Journal: Proteomic analysis of the cardiac myocyte secretome reveals extracellular protective functions for the ER stress response. (Pubmed Central) - Jul 14, 2021 In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume...Mechanistically, secreted GRP78 was shown to enhance survival of NRVMs by collaborating with a cell-surface protein, CRIPTO, to activate protective AKT signaling and to inhibit death-promoting SMAD2 signaling. Thus, proteins secreted during ER stress mediated by ER calcium depletion can enhance cardiac myocyte viability.
- |||||||||| Journal: CRIPTO antagonist ALK4-Fc inhibits breast cancer cell plasticity and adaptation to stress. (Pubmed Central) - Jun 22, 2021
Identifying mechanisms that govern cellular adaptation, plasticity, and the emergence of stem-like cancer cells may be key to effective anticancer therapies. Results presented here indicate that targeting CRIPTO with ALK4-Fc may have potential as such a therapy since it inhibits breast cancer cell adaptation to microenvironmental challenges and associated stem-like and EMT phenotypes.
- |||||||||| Journal: The Role of Nodal and Cripto-1 in Human Oral Squamous Cell Carcinoma. (Pubmed Central) - Jun 16, 2021
Further investigation showed that the combination treatment with both Nodal and CR-1 inhibitors was capable of reducing invasiveness of SCC25 cells. Our results show a possible role for Nodal/CR-1 function during progression of human OSCC and that targeting both proteins simultaneously may have therapeutic potential.
- |||||||||| Review, Journal, Cancer stem cells: Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy. (Pubmed Central) - Jun 3, 2021
In recent years, it has been reported that Cripto-1 could be a potential therapeutic target in CSCs. Here, we review the accumulated literature on the molecular mechanisms by which Cripto-1 functions in CSCs and discuss the potential of Cripto-1 as an immunotherapeutic target in CSCs.
- |||||||||| Journal: Expression and Prognostic Value of Cripto-1 in Pancreatic Cancer (Pubmed Central) - May 11, 2021
Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ =4.787,P=0.029).However,multivariate analysis failed to demonstrate overexpression of Cripto-1 an independent prognostic indicator in patients with pancreatic cancer(HR=1.341,95% CI=0.800-2.248,P=0.266).Conclusions Cripto-1 may play an important role in the development and progression of pancreatic cancer.It can be a potential prognostic biomarker for patients with pancreatic cancer.
- |||||||||| Journal: Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle. (Pubmed Central) - Apr 28, 2021
This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial-to-Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle-infiltrating macrophages, Cripto is required to promote the expansion of the CD206 anti-inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells.
- |||||||||| Journal: A Novel Artificially Humanized Anti-Cripto-1 Antibody Suppressing Cancer Cell Growth. (Pubmed Central) - Apr 13, 2021
Simultaneously, the antibody exhibited the potential to suppress the growth of human colon cancer derived GEO cells overexpressing Cripto-1 with IC at approximately 110 nM. The artificially humanized antibody is proposed to be a good candidate to target cancer cells overexpressing Cripto-1.
- |||||||||| Biomarker, Journal: An evaluation of different Cripto-1 antibodies and their variable results. (Pubmed Central) - Mar 19, 2021
The cripto-1 expression was varied for the different antibodies with respect to cellular localization and fixation methods. To further elaborate on these findings, we present a systematic review of cripto-1 antibodies found in the literature and highlight some possible cross reactants with data on sequence alignments and structural comparison of EGF domains.
- |||||||||| Journal: PGAP6, a GPI-specific phospholipase A2, has narrow substrate specificity against GPI-anchored proteins. (Pubmed Central) - Feb 24, 2021
In this report, chimeras between CRIPTO and CRYPTIC and truncate mutants of PGAP6 were used to demonstrate that the CFC (Cripto-1/FRL1/Cryptic) domain of CRIPTO is recognized by an N-terminal domain of PGAP6 for processing. We also report that among 56 human GPI-anchored proteins tested, only glypican 3, prostasin, SPACA4 and contactin-1 in addition to CRIPTO are sensitive to PGAP6, indicating that PGAP6 has a narrow specificity toward various GPI-anchored proteins.
- |||||||||| Journal: Structure-based design of small bicyclic peptide inhibitors of Cripto-1 activity. (Pubmed Central) - Dec 17, 2020
The functional effects of B3 on the Cripto-1-positive NTERA cancer cell line have been evaluated showing that both CFC and B3 are cytotoxic for the cells and block the Cripto-1 intracellular signaling. Altogether, the data suggest that administration of the soluble CFC and of the structurally related analogue has the potential to inhibit tumor growth.
- |||||||||| Biomarker, Journal: Beneficial effects of Cripto-1 for transarterial chemoembolization in hepatocellular carcinoma. (Pubmed Central) - Jun 19, 2020
In different subgroups of vascular invasion, larger tumor size or liver cirrhosis, patients with adjuvant TACE had longer TTR and OS times than those without TACE in patients with high Cripto-1 expression, while they could not obtain benefits from adjuvant TACE in patients with low-expressed Cripto-1 expression. In conclusion, Cripto-1 may be a potential prognostic factor in predicting outcome of HCC patients with TACE therapy, and combined with Cripto-1 and tumor features may be helpful to stratify patients with respect to prognosis and response to adjuvant TACE.
- |||||||||| Biomarker, Journal: The function and prognostic significance of Cripto-1 in colorectal cancer. (Pubmed Central) - May 11, 2020
Cripto-1-silenced colorectal cancer cell lines had reduced cell proliferation, migration, and activation of Akt and MAPK signaling pathways in vitro, and decreased tumor growth and lymph node metastasis in vivo. Cripto-1 could be a useful prognostic biomarker and therapeutic target in colorectal cancer.
- |||||||||| Journal: Investigating the oxidative refolding mechanism of Cripto-1 CFC domain. (Pubmed Central) - Feb 7, 2020
Data altogether support a mechanism whereby the Cripto-1 CFC domain refolds by virtue of long-range intramolecular interactions that involve residues close to cysteines of the second and third bridge. These findings are supported by the in silico study that shows how distant parts of the molecules come into contact on a long time scale.
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