The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review

Zhang, Qi; Han, Zhenzhen; Zhu, Yanbo; Chen, Jingcheng; Li, Wei

doi:10.15283/ijsc20097

Cited by 54 publications

(39 citation statements)

References 131 publications

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“…Moreover, NNK increases the expression levels of OCT-4, SOX-2, and Nanog, which are thought to play an important role in tumour stem cells. It is consistent with previous research that elevated levels may indicate increased stemness in tumour cells [23][24][25] . Our experiments also con rmed that NNK can promote gemcitabine resistance.…”

Section: Discussionsupporting

confidence: 93%

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

Chen

Zhang

Liu

et al. 2021

Preprint

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Background: Low responsiveness to chemotherapy is an important cause of poor prognosis in pancreatic cancer. Smoking is a high-risk factor for pancreatic cancer and its resistance to gemcitabine; however, the underlying mechanisms remain unclear. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the main metabolite of tobacco burning and has been shown to be associated with cancer development and chemoresistance, but in pancreatic cancer, its mechanism remains poorly understood.Methods: The effect of NNK on pancreatic cancer cell viability was confirmed by using Cell Counting Kit-8 and colony formation assays. Stem cell sphere formation assays and western blotting/qPCR measurements of stemness-related molecules were used to detect pancreatic cancer cell stemness. The pancreatic cancer autophagy status was evaluated by immunofluorescence staining of LC3 and western blotting/qPCR analysis of autophagy-related molecules.Results: NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Furthermore, NNK intervention increased autophagy and changed the expression levels of autophagy-related markers, which preliminarily confirmed the activation of autophagy by NNK. Finally, the results showed that NNK-promoted stemness, and gemcitabine resistance was activated by the autophagy pathway, which was mediated by the β2AR-Akt signalling pathway.Conclusions: Autophagy induced by activating the NNK-induced β2AR-Akt signalling pathway promoted stemness and gemcitabine resistance in pancreatic cancer cells.

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Section: Discussionsupporting

confidence: 93%

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

Chen

Zhang

Liu

et al. 2021

Preprint

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“…When expressed in cancer stem cells, these 3 proteins are capable of interaction that results in tumor development and cancer progression. 9,24…”

Section: Discussionmentioning

confidence: 99%

“…4,5,10,11 These proteins interact in neoplastic cells, especially cancer stem cells, blocking cell differentiation. 9 Studies also demonstrate that these proteins indicate poor prognosis when overexpressed in tumors, including worse overall survival and resistance to treatment. 11 Gliomas have also been linked to these 3 ESC regulatory factors.…”

Section: Introductionmentioning

confidence: 99%

Pediatric Astrocytomas and Their Association With Polymorphisms in Embryonic Stem Cell Marker Genes

et al. 2022

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Background Embryonic stem cell markers, such as SOX2, NANOG, and OCT4, are transcription factors expressed in pluripotent stem cells, involved in the mediation of pluripotency and self-renewal. Especially after the discovery of cancer stem cells, these proteins have been associated with several types of neoplasia, including astrocytomas. In the pediatric population, astrocytomas are the most common solid neoplasia and present the highest mortality rates. Methods Our study evaluated 5 polymorphisms in SOX2, NANOG, and POU5F1 genes in 101 pediatric astrocytoma samples. Results We describe the associations between wild and polymorphic alleles in astrocytomas. Conclusions In our results, the intronic polymorphic G allele in SOX2 rs77677339 [G/A] had a borderline association with low-grade astrocytomas, and the intronic polymorphic T allele in NANOG rs10845877 [C/T] showed a higher frequency in grade 2, compared to grade 1 astrocytomas, thus showing promising results. Impact Our study is relevant because it shows a potential correlation between polymorphic embryonic stem cell marker genes and pediatric astrocytomas.

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“…Pseudogenes, like OCT4-PG1, are also implicated in cancer as the over-expression of this gene promotes tumorigenicity in vitro and in vivo , consistent with the association of OCT4-PG1 over-expression and poor prognosis in gastric cancer ( Hayashi et al, 2015 ). In spite of the confusion regarding the isoforms and pseudogenes of OCT4 expressed in CSCs, many studies show the importance of the molecule in CSC characteristics ( Zhang et al, 2020 ). The signaling event leading to the regulation of OCT4 expression and its downstream targets, regulating CSC characteristics, are summarized in Figure 6 .…”

Section: Markers Of Cscsmentioning

confidence: 99%

Markers and Reporters to Reveal the Hierarchy in Heterogeneous Cancer Stem Cells

Mohan

Rajan

Mohan

et al. 2021

Front. Cell Dev. Biol.

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A subpopulation within cancer, known as cancer stem cells (CSCs), regulates tumor initiation, chemoresistance, and metastasis. At a closer look, CSCs show functional heterogeneity and hierarchical organization. The present review is an attempt to assign marker profiles to define the functional heterogeneity and hierarchical organization of CSCs, based on a series of single-cell analyses. The evidences show that analogous to stem cell hierarchy, self-renewing Quiescent CSCs give rise to the Progenitor CSCs with limited proliferative capacity, and later to a Progenitor-like CSCs, which differentiates to Proliferating non-CSCs. Functionally, the CSCs can be tumor-initiating cells (TICs), drug-resistant CSCs, or metastasis initiating cells (MICs). Although there are certain marker profiles used to identify CSCs of different cancers, molecules like CD44, CD133, ALDH1A1, ABCG2, and pluripotency markers [Octamer binding transcriptional factor 4 (OCT4), SOX2, and NANOG] are used to mark CSCs of a wide range of cancers, ranging from hematological malignancies to solid tumors. Our analysis of the recent reports showed that a combination of these markers can demarcate the heterogeneous CSCs in solid tumors. Reporter constructs are widely used for easy identification and quantification of marker molecules. In this review, we discuss the suitability of reporters for the widely used CSC markers that can define the heterogeneous CSCs. Since the CSC-specific functions of CD44 and CD133 are regulated at the post-translational level, we do not recommend the reporters for these molecules for the detection of CSCs. A promoter-based reporter for ABCG2 may also be not relevant in CSCs, as the expression of the molecule in cancer is mainly regulated by promoter demethylation. In this context, a dual reporter consisting of one of the pluripotency markers and ALDH1A1 will be useful in marking the heterogeneous CSCs. This system can be easily adapted to high-throughput platforms to screen drugs for eliminating CSCs.

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The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review

Cited by 54 publications

References 131 publications

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

Pediatric Astrocytomas and Their Association With Polymorphisms in Embryonic Stem Cell Marker Genes

Markers and Reporters to Reveal the Hierarchy in Heterogeneous Cancer Stem Cells

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