Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

Piazzolla, Daniela; Palla, Adelaida; Pantoja, Cristina; Cañamero, Marta; Castro, Ignacio Pérez de; Ortega, Sagrario; Gómez‐López, Gonzalo; Domı́nguez, Orlando; Megı́as, Diego; Roncador, Giovanna; Luque-García, José L.; Fernandez-Tresguerres, Beatriz; Fernández, Agustín F.; Fraga, Mario F.; Rodriguez‐Justo, Manuel; Manzanares, Miguel; Sänchez‐Carbayo, Marta; García-Pedrero, Juana M.; Malumbres, Marcos; Serrano, Manuel

doi:10.1038/ncomms5226

Cited by 49 publications

(68 citation statements)

References 64 publications

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“…Findings from others and us that Nanog initiates distinct oncogenic transcriptional programs in different tissues could contribute to the diversified oncogenic roles of Nanog in the mammary gland and skin. 23 By expressing a Nanog pseudogene NANOGP8 in the mouse skin, it inhibits the skin tumorigenesis induced by chemical carcinogen, suggesting that Nanog might be a tumor suppressor. 33 Our findings that Nanog activates p53 in the skin cells to induce the differentiation of progenitor cells could explain this apparent discrepancy.…”

Section: Nanog Induces Dna Dsb Damage and Inactivates Kap1mentioning

confidence: 99%

Pluripotency factor Nanog is tumorigenic by deregulating DNA damage response in somatic cells

et al. 2015

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The pluripotency gene Nanog is not expressed in normal adult tissues but is overexpressed in some human cancers. However, the tumorigenic roles of Nanog remain unclear. The ectopic expression of Nanog is not sufficient to induce spontaneous tumors in mice but can promote metastasis of established tumors by activating the expression of metastatic genes. The expression of Nanog in mouse skin activates tumor suppressor p53, leading to the differentiation of epidermal stem cells. In the absence of p53, Nanog induces spontaneous squamous cell carcinoma, identifying a novel role of Nanog in tumorigenesis. Therefore, the induction of p53 and differentiation in Nanog-expressing skin suppresses the tumorigenic activities of Nanog, which include the induction of DNA double-stranded break damage. Notably, Nanog interacts with the KRAB-associated protein 1 (KAP1) and inhibits its sumoylation activity, impairing KAP1-mediated chromatin remodeling, which is important for efficiently activating DNA damage response. In summary, Nanog is an oncogene with multiple roles in promoting tumorigenesis and metastasis.

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Section: Nanog Induces Dna Dsb Damage and Inactivates Kap1mentioning

confidence: 99%

Pluripotency factor Nanog is tumorigenic by deregulating DNA damage response in somatic cells

et al. 2015

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“…More recently, Nanog was also shown to regulate cell division in stratified epithelia in adult organisms (Piazzolla et al, 2014).…”

Section: ) Osteogenesis Is Induced By Expression Of Runx2mentioning

confidence: 99%

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes

et al. 2017

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Fractures heal predominantly through the process of endochondral ossification. The classic model of endochondral ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate that chondrocytes transdifferentiate to osteoblasts in the growth plate and during regeneration, yet the mechanism(s) regulating this process remain unknown. Here, we show a spatiallydependent phenotypic overlap between hypertrophic chondrocytes and osteoblasts at the chondro-osseous border in the fracture callus, in a region we define as the transition zone (TZ). Hypertrophic chondrocytes in the TZ activate expression of the pluripotency factors [Sox2, Oct4 (Pou5f1), Nanog], and conditional knock-out of Sox2 during fracture healing results in reduction of the fracture callus and a delay in conversion of cartilage to bone. The signal(s) triggering expression of the pluripotency genes are unknown, but we demonstrate that endothelial cell conditioned medium upregulates these genes in ex vivo fracture cultures, supporting histological evidence that transdifferentiation occurs adjacent to the vasculature. Elucidating the cellular and molecular mechanisms underlying fracture repair is important for understanding why some fractures fail to heal and for developing novel therapeutic interventions.

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“…It has become the sixth leading cause of death and the eighth most frequently diagnosed cancer [1][2][3]. Esophageal carcinoma includes two main types: esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma [4,5]. ESCC is the most common subtype with a poor treatment and survive rate with a 5-year overall survival rate about 14% [6,7].…”

Section: Introductionmentioning

confidence: 99%

Three Circulating LncRNA Predict Early Progress of Esophageal Squamous Cell Carcinoma

Zheng

2016

Cell Physiol Biochem

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Background/Aims: Previous studies revealed that circulating (either from plasma or serum) long non-coding RNA may predict the occurrence or prognosis of multiple human malignant tumors. In this study, we mainly explored whether circulating lncRNAs can be utilized as biomarkers predicting the development of human esophageal squamous cell carcinoma (ESCC). Methods: LncRNA microarray was applied to screen the potential biomarkers for ESCC. Each group contained three individual plasma samples. A multi-stage validation and risk score formula detection were used for validation. Results: Eleven dysregulated lncRNAs were obtained after Venny analysis. Further validation in a larger cohort including 205 ESCC patients, 82 patients suffering from esophagus dysplasia and 210 healthy controls confirmed that increased Linc00152, CFLAR-AS1 and POU3F3 might be potential biomarkers for predicting the early progress with an area under curve (AUC) of 0.698, 0.651 and 0.584, respectively. The merged AUC of the three factors and merged with CEA was 0.765 and 0.955, respectively. We also revealed that circulating levels of three lncRNAs were associated with poor post-surgery prognosis of ESCC patients. Conclusions: The three circulating lncRNAs might serve as potential biomarkers for predicting the early occurrence of ESCC.

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Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

Cited by 49 publications

References 64 publications

Pluripotency factor Nanog is tumorigenic by deregulating DNA damage response in somatic cells

Pluripotency factor Nanog is tumorigenic by deregulating DNA damage response in somatic cells

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes

Three Circulating LncRNA Predict Early Progress of Esophageal Squamous Cell Carcinoma

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