Concise Review: Pursuing Self-Renewal and Pluripotency with the Stem Cell Factor Nanog

Saunders, Arven; Faiola, Francesco; Wang, Jianlong

doi:10.1002/stem.1384

Cited by 95 publications

(82 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2a,b). Of note, adult tissues presented two bands in the electrophoretic gels, which is in line with the complexity of NANOG transcriptional isoforms and post-transcriptional modifications 24 .…”

supporting

confidence: 73%

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

et al. 2014

View full text Add to dashboard Cite

NANOG is a pluripotency transcription factor in embryonic stem cells; however, its role in adult tissues remains largely unexplored. Here we show that mouse NANOG is selectively expressed in stratified epithelia, most notably in the oesophagus where the Nanog promoter is hypomethylated. Interestingly, inducible ubiquitous overexpression of NANOG in mice causes hyperplasia selectively in the oesophagus, in association with increased cell proliferation. NANOG transcriptionally activates the mitotic programme, including Aurora A kinase (Aurka), in stratified epithelia, and endogenous NANOG directly binds to the Aurka promoter in primary keratinocytes. Interestingly, overexpression of Nanog or Aurka in mice increased proliferation and aneuploidy in the oesophageal basal epithelium. Finally, inactivation of NANOG in cell lines from oesophageal or head and neck squamous cell carcinomas (ESCCs or HNSCCs, respectively) results in lower levels of AURKA and decreased proliferation, and NANOG and AURKA expression are positively correlated in HNSCCs. Together, these results indicate that NANOG has a lineage-restricted mitogenic function in stratified epithelia.

show abstract

supporting

confidence: 73%

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

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Moreover, BBI608 significantly reduced the expression of various stemness genes, including Nanog, Sox2, and Oct4 (POU5F1). These genes encode key stemness transcription factors that are important for the maintenance of pluripotency (36,37). These data demonstrate the feasibility of inhibiting cancer stemness by modulating stemness gene expression.…”

Section: Discussionmentioning

confidence: 79%

Suppression of cancer relapse and metastasis by inhibiting cancer stemness

Rogoff

Keates

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

400

366

View full text Add to dashboard Cite

Partial or even complete cancer regression can be achieved in some patients with current cancer treatments. However, such initial responses are almost always followed by relapse, with the recurrent cancer being resistant to further treatments. The discovery of therapeutic approaches that counteract relapse is, therefore, essential for advancing cancer medicine. Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types. Moreover, such stemness-high cancer cells are resistant to conventional chemotherapy and radiation. Here we show that BBI608, a small molecule identified by its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties, can inhibit stemness gene expression and block spherogenesis of or kill stemnesshigh cancer cells isolated from a variety of cancer types. Moreover, cancer relapse and metastasis were effectively blocked by BBI608 in mice. These data demonstrate targeting cancer stemness as a novel approach to develop the next generation of cancer therapeutics to suppress cancer relapse and metastasis.cancer stemness | relapse | BBI608 C urrent cancer treatments ultimately fail owing to metastasis and relapse. Although chemotherapy can induce partial or even complete cancer regression in some patients, such initial responses are invariably followed by relapse, with the recurrent cancer being highly resistant to further chemotherapy, resulting in very limited survival benefits (1-3). Modern therapeutics designed to specifically target activating mutations are quite effective in inducing cancer regression in patients driven by such activating mutations; however, these treatments are also invariably followed by relapse with tumors that no longer respond to the targeted agent (2, 3). The discovery of novel therapeutic approaches that counteract cancer relapse is, therefore, urgently required for advancing cancer treatment.The idea that cancer is composed of a group of near-homogenous, ectopically growing cells has been replaced with a more complex model in which cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential to metastasize and cause relapse. The increased understanding of the genomic and proteomic complexity of tumor heterogeneity further highlights the extreme heterogeneity of cancer cells (4).Subpopulations of cancer cells with extremely high tumorigenic potential, termed cancer stem cells or stem-like cancer cells, have been isolated from cancer patients with a variety of tumor types (5-13) and found to have high stemness properties (5-15). Stemness, initially defined by the expression of stem cells genes, is a property shared by embryonic stem cells and adult stem cells (16). In ...

show abstract

“…NANOG, a homeodomain transcription factor found in many pluripotent cells (Saunders et al, 2013), was not detected in the posterior region of the mouse conceptus until E7.75, when, based on sectional analysis, it localized to $50% of cells exhibiting STELLA protein . By E8.5, however, when the PGC population had translocated into the hindgut endoderm, $90% of STELLA-positive endodermal cells colocalized NANOG .…”

Section: Nanogmentioning

confidence: 98%