Role of Hexosamine Biosynthetic Pathway on Cancer Stem Cells: Connecting Nutrient Sensing to Cancer Cell Plasticity

2021 ◽  
Author(s):  
Giang Le Minh ◽  
Mauricio J. Reginato
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cell ◽  
Biosynthetic Pathway ◽  
Nutrient Sensing ◽  
Cell Plasticity ◽  
Hexosamine Biosynthetic Pathway

scholarly journals LncRNA ASAP1-IT1 enhances cancer cell stemness via regulating miR-509-3p/YAP1 axis in NSCLC

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yantao Liu ◽  
Yuping Yang ◽  
Lingli Zhang ◽  
Jiaqiang Lin ◽  
Bin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Qrt Pcr

Abstract Background Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. Methods The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. Results ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. Conclusions YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.

scholarly journals Targeting multiple genes containing long mononucleotide A-T repeats in lung cancer stem cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Narumol Bhummaphan ◽  
Piyapat Pin-on ◽  
Preeyaporn Plaimee Phiboonchaiyanan ◽  
Jirattha Siriluksana ◽  
Chatchawit Aporntewan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cell ◽  
Transcriptional Control ◽  
Single Gene ◽  
Repeat Sequence ◽  
Control Activity ◽  
Multiple Genes ◽  
Lung Cancer Stem Cells

Abstract Background Intratumour heterogeneous gene expression among cancer and cancer stem cells (CSCs) can cause failure of current targeted therapies because each drug aims to target the function of a single gene. Long mononucleotide A-T repeats are cis-regulatory transcriptional elements that control many genes, increasing the expression of numerous genes in various cancers, including lung cancer. Therefore, targeting A-T repeats may dysregulate many genes driving cancer development. Here, we tested a peptide nucleic acid (PNA) oligo containing a long A-repeat sequence [A(15)] to disrupt the transcriptional control of the A-T repeat in lung cancer and CSCs. Methods First, we separated CSCs from parental lung cancer cell lines. Then, we evaluated the role of A-T repeat gene regulation by counting the number of repeats in differentially regulated genes between CSCs and the parental cells of the CSCs. After testing the dosage and effect of PNA-A15 on normal and cancer cell toxicity and CSC phenotypes, we analysed genome-wide expression to identify dysregulated genes in CSCs. Results The number of A-T repeats in genes differentially regulated between CSCs and parental cells differed. PNA-A15 was toxic to lung cancer cells and CSCs but not to noncancer cells. Finally, PNA-A15 dysregulated a number of genes in lung CSCs. Conclusion PNA-A15 is a promising novel targeted therapy agent that targets the transcriptional control activity of multiple genes in lung CSCs.

scholarly journals Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1674
Author(s):  
Sara Tomei ◽  
Ola Ibnaof ◽  
Shilpa Ravindran ◽  
Soldano Ferrone ◽  
Cristina Maccalli
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Aberrant Expression ◽  
Immunological Profile ◽  
Malignant Lesions ◽  
Novel Therapeutic Strategies ◽  
Antigen Processing And Presentation

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

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

Cancers ◽  
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.

scholarly journals Glioma Revisited: From Neurogenesis and Cancer Stem Cells to the Epigenetic Regulation of the Niche

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Felipe de Almeida Sassi ◽  
Algemir Lunardi Brunetto ◽  
Gilberto Schwartsmann ◽  
Rafael Roesler ◽  
Ana Lucia Abujamra
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cellular Proliferation ◽  
Survival Rates ◽  
Comprehensive Analysis ◽  
Heterogeneous Population ◽  
Aggressive Tumor ◽  
Epigenetic Modulation ◽  
The Brain

Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment.

scholarly journals Cancer stem cells and cisplatin‐resistant cells isolated from non‐small‐lung cancer cell lines constitute related cell populations

2014 ◽  
Vol 3 (5) ◽  
pp. 1099-1111 ◽  
Author(s):  
Blanca D. Lopez‐Ayllon ◽  
Veronica Moncho‐Amor ◽  
Ander Abarrategi ◽  
Inmaculada Ibañez Cáceres ◽  
Javier Castro‐Carpeño ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cell Populations ◽  
Lung Cancer Cell ◽  
Related Cell ◽  
Resistant Cells

scholarly journals Role of p38γ MAPK in regulation of EMT and cancer stem cells

2018 ◽  
Vol 1864 (11) ◽  
pp. 3605-3617 ◽  
Author(s):  
Mei Xu ◽  
Siying Wang ◽  
Yongchao Wang ◽  
Huaxun Wu ◽  
Jacqueline A. Frank ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells

scholarly journals The role of steroid hormones in breast cancer stem cells

2015 ◽  
Vol 22 (6) ◽  
pp. T177-T186 ◽  
Author(s):  
Bruno M Simões ◽  
Denis G Alferez ◽  
Sacha J Howell ◽  
Robert B Clarke
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Steroid Hormones ◽  
Normal Mammary Gland ◽  
Breast Cancer Stem Cells ◽  
Tumor Initiating Cells ◽  
Unit Of Selection ◽  
Selection For

Breast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity.

Abstract 1083: A novel role of SRC in mediating bypass resistance to MEK inhibition in colorectal cancer stem cells

2021 ◽  
Author(s):  
Mingli Yang ◽  
Thomas B. Davis B. Davis ◽  
Michael V. Nebozhyn ◽  
Andrey Loboda ◽  
Heiman Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Mek Inhibition ◽  
Colorectal Cancer Stem Cells
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