Novel Roles of Nanog in Cancer Cells and Their Extracellular Vesicles

Abstract

The use of extracellular vesicle (EV)-based vaccines is a strategically promising way to prevent cancer metastasis. The effective roles of immune cell-derived EVs have been well understood in the literature. In the present paper, we focus on cancer cell-derived EVs to enforce, more thoroughly, the use of EV-based vaccines against unexpected malignant cells that might appear in poor prognostic patients. As a model of such a cancer cell with high malignancy, Nanog-overexpressing melanoma cell lines were developed. As expected, Nanog overexpression enhanced the metastatic potential of melanomas. Against our expectations, a fantastic finding was obtained that determined that EVs derived from Nanog-overexpressing melanomas exhibited a metastasis-suppressive effect. This is considered to be a novel role for Nanog in regulating the property of cancer cell-derived EVs. Stimulated by this result, the review of Nanog’s roles in various cancer cells and their EVs has been updated once again. Although there was no other case presenting a similar contribution by Nanog, only one case suggested that NANOG and SOX might be better prognosis markers in head and neck squamous cell carcinomas. This review clarifies the varieties of Nanog-dependent phenomena and the relevant signaling factors. The information summarized in this study is, thus, suggestive enough to generate novel ideas for the construction of an EV-based versatile vaccine platform against cancer metastasis.

Analysis of Glucose Uptake by Highly Metastatic <i>Nanog</i>-overexpressing Melanoma Cells Using Fluorescent Glucose Analogs

“…8 We developed an Nanog overexpressing melanoma cell line (Nanog + BL6) because undifferentiation statemaintaining factors such as Nanog are well correlated with cancer malignancy. 9 Transcriptome analysis revealed the up-regulated and down-regulated genes in Nanog + BL6 as compared to BL6. Slc37a4 was the top up-regulated gene, followed by mitochondrial oxidative phosphorylation-related genes such as mt-Atp6, mt-Nd3, mt-Co3, mt-Atp8, and mt-Co2.…”

Suppression of Metastasis of Colon Cancer to Liver by Pretreatment With Extracellular Vesicles Derived From Nanog-Overexpressing Colon Cancer Cells

“…A positive correlation was observed between the expression levels of Nanog and the malignancy levels in 14 types of cancer, including breast cancer, colon cancer, embryonal carcinoma, liver cancer, and skin cancer (melanoma) [14][15][16]. Melanoma and its metastasis to the liver were selected as the initial target cancer.…”

Comparative Study of Metastasis Suppression Effects of Extracellular Vesicles Derived from Anaplastic Cell Lines, Nanog-Overexpressing Melanoma, and Induced Pluripotent Stem Cells

“…However, while EVs derived from the original melanoma cell line, B16-F10 (F10 EVs), showed a metastasis-promoting effect, EVs derived from the Nanog-overexpressing melanoma cell line (Nanog + F10) (Nanog + F10 EVs) showed a metastasis-suppressive effect [18]. There have already been many reports regarding the correlation between Nanog and the malignant transformation of cancer cells [19][20][21]. In 14 out of 15 types of cancer including breast cancer, colon cancer, large intestine cancer, liver cancer, and skin cancer (melanoma), the higher the expression level of Nanog (NANOG), the higher the malignancy of the cancer cells (in vitro proliferation ability, migration ability, invasion ability, drug resistance, and in vivo metastatic ability).…”