Role of Cripto-1 in Stem Cell Maintenance and Malignant Progression

Abstract

Cripto-1 is critical for early embryonic development and, together with its ligand Nodal, has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Like other embryonic genes, Cripto-1 performs important roles in the formation and progression of several types of human tumors, stimulating cell proliferation, migration, epithelial to mesenchymal transition, and tumor angiogenesis. Several studies have demonstrated that cell fate regulation during embryonic development and cell transformation during oncogenesis share common signaling pathways, suggesting that uncontrolled activation of embryonic signaling pathways might drive cell transformation and tumor progression in adult tissues. Here we review our current understanding of how Cripto-1 controls stem cell biology and how it integrates with other major embryonic signaling pathways. Because many cancers are thought to derive from a subpopulation of cancer stem-like cells, which may re-express embryonic genes, Cripto-1 signaling may drive tumor growth through the generation or expansion of tumor initiating cells bearing stem-like characteristics. Therefore, the Cripto-1/Nodal signaling may represent an attractive target for treatment in cancer, leading to the elimination of undifferentiated stem-like tumor initiating cells.

Investigational antibody drug conjugates for solid tumors

“…Cripto, the therapeutic target, is a cell membrane anchored GPI (glycosyl-phosphatidylinositol)-linked glycoprotein and is the original member of the epidermal growth factor-Cripto-FRL-Criptic (EGF-CFC) family. Cripto plays an important role in embryonic development and in tumor progression (reviewed in [37]). Interestingly, Cripto is a key molecule in the signaling transduction pathways of TGF-beta superfamily members, particularly required for signal transduction of the TGF-beta ligand, Nodal.…”

Identification of Cancer Stem Cells in Oral Squamous Cell Carcinoma Using Cripto-1.

“…Although the CR-1 protein was over expressed in several human cancers including breast, colon, cervix, gastric, and pancreatic cancer (Bianco et al, 2010 andFrancescangeli et al, 2015), no one shed the light on its importance as a novel marker for CSC and to the best of our knowledge, only one study evaluated CR-1 expression in OSCC . Therefore, the current work investigated the CR-1 expression in clinical samples of OSCC using immunoflurescence, to analyze the correlation between CR-1 expression as a CSC marker and the different grades in OSCC.…”

The Construction and Identification of Induced Pluripotent Stem Cells Derived from Acute Myelogenous Leukemia Cells

“…Lin28 plays an important role in the growth and metabolism of stem cells [34]. Cripto plays an important part in maintaining the undifferentiated state of stem cells but is also a key gene in the early development of embryos [35]. DNMT3b is a type of methyltransferase that mediates DNA methylation and plays an important role in the growth and development of embryonic stem cells [36].…”