The expression of the embryonic gene Cripto‐1 is regulated by <scp>OCT</scp>4 in human embryonal carcinoma <scp>NCCIT</scp> cells

Park, Sung-Won; Do, Hyun-Jin; Han, Mi-Hee; Choi, Wonbin; Kim, Jaehwan

doi:10.1002/1873-3468.12935

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…Interestingly, they found that Nanog and Oct4, two transcription factors (TFs) highly active in stem cells [64,65], bind CR-1 promoter and induce its transcription. This evidence was also confirmed by another group in the same cancer type [66]. However, silencing of CR-1 in these cells does not significantly alter the expression of Oct4 and Nanog, suggesting the existence of a Cripto-independent pathway that sustains the expression of these stem TFs.…”

Section: The Role Of Nodal and Cripto-1 In Cancer Stem Cellssupporting

confidence: 75%

New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates

Arboretto

Cillo

Leonardi

2021

IJMS

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The transforming growth factor beta (TGF-β) signaling is fundamental for correct embryonic development. However, alterations of this pathway have been correlated with oncogenesis, tumor progression and sustaining of cancer stem cells (CSCs). Cripto-1 (CR-1) and Nodal are two embryonic proteins involved in TGF-β signaling. Their expression is almost undetectable in terminally differentiated cells, but they are often re-expressed in tumor cells, especially in CSCs. Moreover, cancer cells that show high levels of CR-1 and/or Nodal display more aggressive phenotypes in vitro, while in vivo their expression correlates with a worse prognosis in several human cancers. The ability to target CSCs still represents an unmet medical need for the complete eradication of certain types of tumors. Given the prognostic role and the selective expression of CR-1 and Nodal on cancer cells, they represent archetypes for targeted therapy. The aim of this review is to clarify the role of CR-1 and Nodal in cancer stem populations and to summarize the current therapeutic strategy to target CSCs using monoclonal antibodies (mAbs) or other molecular tools to interfere with these two proteins.

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Section: The Role Of Nodal and Cripto-1 In Cancer Stem Cellssupporting

confidence: 75%

New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates

Arboretto

Cillo

Leonardi

2021

IJMS

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“…Cripto-1, also known as teratocarcinoma-derived growth factor1 (TDGF-1), is a member of the epidermal growth factor/Cripto-1-FRL-1-Cryptic family ( 7 ). It is isolated and cloned from the human teratocarcinoma cDNA library of NTERA-2, and is indispensable for early embryonic development and maintenance of the pluripotency of embryonic stem cells ( 8 ). Recently, Cripto-1 has been reported to be an oncogene that plays an important role in the initiation and progression of several types of human cancers ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Exosomal Cripto-1 Serves as a Potential Biomarker for Perihilar Cholangiocarcinoma

Zhang

et al. 2021

Front. Oncol.

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Perihilar cholangiocarcinoma (PHCCA) has a poor prognosis, mainly due to diagnosis at an advanced stage. Cripto-1 functions as an oncogene and is highly expressed in several human cancers, however, its clinical application in PHCCA is poorly understood. Herein, we identified that Cripto-1 was released by PHCCA cells via exosomes in vitro and in vivo. Furthermore, an ELISA method was developed to detect exosomal Cripto-1 in the serum of 115 PHCCA patients, 47 cholangitis patients and 65 healthy controls, and it was found that exosomal Cripto-1 was increased in PHCCA patients and associated with metastasis. Compared with traditional serum tumor markers, CA19-9 and CEA, exosomal Cripto-1 demonstrated a larger area under ROC curve for PHCCA diagnosis. The cutoff value of exosomal Cripto-1 was 0.82, achieving a sensitivity of 79.1% and a specificity of 87.5%. As expected, exosomal Cripto-1 levels in immunohistochemically Cripto-1-high cases were significantly elevated compared to in Cripto-1-low cases. When measured 1-week postoperatively, Cripto-1 levels decreased on average from 1.25(0.96-3.26) to 0.85(0.62-1.82). Immunohistochemistry analysis showed Cripto-1 expression was negatively correlated with E-cadherin and was an independent prognostic biomarker for poor survival in PHCCA patients. In conclusion, exosomal Cripto-1 in sera can reflect its expression in the tissue of PHCAA patients and has the potential be a non-invasive biomarker for diagnosis and prognosis of PHCCA.

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“…This might be associated with the EMT gene expression program of CSCs to support their abilities in self-renewal, invasion, and metastasis. In one study, the stemnessrelated transcription factors, Nanog and Oct4, modulated Cripto-1 expression [37]. In another study, Cripto-1 was found to be essential for triggering and maintaining the expression of Nanog and Oct4 [38].…”

Section: Discussionmentioning

confidence: 98%

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway

Tsai

et al. 2021

Molecules

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Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in Taraxacum officinale extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.

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The expression of the embryonic gene Cripto‐1 is regulated by OCT4 in human embryonal carcinoma NCCIT cells

Cited by 8 publications

References 42 publications

New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates

New Insights into Cancer Targeted Therapy: Nodal and Cripto-1 as Attractive Candidates

Exosomal Cripto-1 Serves as a Potential Biomarker for Perihilar Cholangiocarcinoma

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway

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