Impact of OCT4 and Its Related Signaling Pathways on Gastrointestinal Cancers: Focusing on Targeted Therapy

There are many pieces of evidence support the effect of cancer stem cells on the initiation and progression of cancer. However, related mechanisms involved in these phenomena are far more complicated to understand. The function of different stemness factorsin cancer stem cells (CSCs) and their complex associations at different levels of cancer have been reported. Therefore, it seems that focusing on one master factor would be more helpful to complete the puzzle of singling pathways in these cells. Octamer-binding transcription factor 4 (OCT4) also known as POU domain, class 5, transcription factor 1(POU5F1), one of these key pluripotency factors, has important roles in both embryogenesis and tumorigenesis. In this review, we gathered information about the association of different markers with OCT4 expression in three types of gastrointestinal cancers including esophageal, gastric and colorectal cancers. OCT4 through different signaling pathways has an impact on different processes of gastrointestinal cancers such as proliferation, invasion, and metastasis. Based on the literature, OCT4 has great effects on cancer progression at different stages, therefore we suggested it has potential implications in therapeutic options.

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The effects of mutant Ras proteins on the cell signalome

Cancer and Metastasis Reviews ◽

10.1007/s10555-020-09912-8 ◽

2020 ◽

Vol 39 (4) ◽

pp. 1051-1065 ◽

Cited By ~ 1

Author(s):

Tamás Takács ◽

Gyöngyi Kudlik ◽

Anita Kurilla ◽

Bálint Szeder ◽

László Buday ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Signaling Pathways ◽

Cancer Progression ◽

Cell Types ◽

Genetic Alterations ◽

Signaling Networks ◽

Specific Cell ◽

Ras Proteins ◽

Ras Genes

AbstractThe genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells.

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Inhibition of C-terminal binding protein attenuates transcription factor 4 signaling to selectively target colon cancer stem cells

Cell Cycle ◽

10.4161/15384101.2014.958407 ◽

2014 ◽

Vol 13 (22) ◽

pp. 3506-3518 ◽

Cited By ~ 11

Author(s):

Jagrut Patel ◽

Somesh Baranwal ◽

Ian M Love ◽

Nirmita J Patel ◽

Steven R Grossman ◽

...

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Transcription Factor ◽

Cancer Stem Cells ◽

Binding Protein ◽

Colon Cancer Stem Cells ◽

Transcription Factor 4

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Modaline sulfate promotes Oct4 expression and maintains self-renewal and pluripotency of stem cells through JAK/STAT3 and Wnt signaling pathways

Cell & Bioscience ◽

10.1186/s13578-021-00669-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xianglin Mei ◽

Hanhan Zhao ◽

Huihan Ai ◽

Shuyue Wang ◽

Zhenbo Song ◽

...

Keyword(s):

Stem Cells ◽

Transcription Factor ◽

Signaling Pathways ◽

P19 Cells ◽

Self Renewal ◽

Oct4 Expression ◽

Pluripotency Markers ◽

Teratoma Formation ◽

Mes Cells

Abstract Background Stem cells have been extensively explored for a variety of regenerative medical applications and they play an important role in clinical treatment of many diseases. However, the limited amount of stem cells and their tendency to undergo spontaneous differentiation upon extended propagation in vitro restrict their practical application. Octamer-binding transcription factor-4 (Oct4), a transcription factor belongs to the POU transcription factor family Class V, is fundamental for maintaining self-renewal ability and pluripotency of stem cells. Methods In the present study, we used the previously constructed luciferase reporters driven by the promoter and 3’-UTR of Oct4 respectively to screen potential activators of Oct4. Colony formation assay, sphere-forming ability assay, alkaline phosphatase (AP) activity assay and teratoma-formation assay were used to assess the role of modaline sulfate (MDLS) in promoting self-renewal and reinforcing pluripotency of P19 cells. Immunofluorescence, RT-PCR, and western blotting were used to measure expression changes of stem-related genes and activation of related signaling pathways. Results We screened 480 commercially available small-molecule compounds and discovered that MDLS greatly promoted the expression of Oct4 at both mRNA and protein levels. Moreover, MDLS significantly promoted the self-renewal capacity of P19 cells. Also, we observed that the expression of pluripotency markers and alkaline phosphatase (AP) increased significantly in MDLS-treated colonies. Furthermore, MDLS could promote teratoma formation and enhanced differentiation potential of P19 cells in vivo. In addition, we found that in the presence of LIF, MDLS could replace feeder cells to maintain the undifferentiated state of OG2-mES cells (Oct4-GFP reporter gene mouse embryonic stem cell line), and the MDLS-expanded OG2-mES cells showed an elevated expression levels of pluripotency markers in vitro. Finally, we found that MDLS promoted Oct4 expression by activating JAK/STAT3 and classic Wnt signaling pathways, and these effects were reversed by treatment with inhibitors of corresponding signaling pathways. Conclusions These findings demonstrated, for the first time, that MDLS could maintain self-renewal and pluripotency of stem cells.

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Hypoxia and Inflammation in Prostate Cancer Progression. Cross-talk with Androgen and Estrogen Receptors and Cancer Stem Cells

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530316666161130160144 ◽

2017 ◽

Vol 16 (4) ◽

pp. 235-248 ◽

Cited By ~ 5

Author(s):

Matteo Russo ◽

Linda Ravenna ◽

Laura Pellegrini ◽

Elisa Petrangeli ◽

Luisa Salvatori ◽

...

Keyword(s):

Prostate Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Estrogen Receptors ◽

Cancer Progression ◽

Cross Talk ◽

Prostate Cancer Progression

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Comprehensive assessment of PD-L1 and PD-L2 dysregulation in gastrointestinal cancers

Epigenomics ◽

10.2217/epi-2020-0093 ◽

2020 ◽

Author(s):

Qijie Zhao ◽

Jinan Guo ◽

Yueshui Zhao ◽

Jing Shen ◽

Parham Jabbarzadeh Kaboli ◽

...

Keyword(s):

Transcription Factor ◽

Signaling Pathways ◽

Underlying Mechanism ◽

Comprehensive Analysis ◽

The Cancer Genome Atlas ◽

Gastrointestinal Cancers ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

Cancer Genome Atlas ◽

Genome Atlas

Background: PD-L1 and PD-L2 are ligands of PD-1. Their overexpression has been reported in different cancers. However, the underlying mechanism of PD-L1 and PD-L2 dysregulation and their related signaling pathways are still unclear in gastrointestinal cancers. Materials & methods: The expression of PD-L1 and PD-L2 were studied in The Cancer Genome Atlas and Genotype-Tissue Expression databases. The gene and protein alteration of PD-L1 and PD-L2 were analyzed in cBioportal. The direct transcription factor regulating PD-L1/ PD-L2 was determined with ChIP-seq data. The association of PD-L1/PD-L2 expression with clinicopathological parameters, survival, immune infiltration and tumor mutation burden were investigated with data from The Cancer Genome Atlas. Potential targets and pathways of PD-L1 and PD-L2 were determined by protein enrichment, WebGestalt and gene ontology. Results: Comprehensive analysis revealed that PD-L1 and PD-L2 were significantly upregulated in most types of gastrointestinal cancers and their expressions were positively correlated. SP1 was a key transcription factor regulating the expression of PD-L1. Conclusion: Higher PD-L1 or PD-L2 expression was significantly associated with poor overall survival, higher tumor mutation burden and more immune and stromal cell populations. Finally, HIF-1, ERBB and mTOR signaling pathways were most significantly affected by PD-L1 and PD-L2 dysregulation. Altogether, this study provided comprehensive analysis of the dysregulation of PD-L1 and PD-L2, its underlying mechanism and downstream pathways, which add to the knowledge of manipulating PD-L1/PD-L2 for cancer immunotherapy.

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The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽

10.3390/cancers13061239 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1239

Author(s):

Leila Jahangiri ◽

Tala Ishola ◽

Perla Pucci ◽

Ricky M. Trigg ◽

Joao Pereira ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Progression ◽

Regulatory Networks ◽

Epithelial To Mesenchymal Transition ◽

Tumour Microenvironment ◽

Repair Capacity ◽

Mesenchymal Transition ◽

Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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