New insights into the pathogenesis and treatment of peritoneal fibrosis: A potential role of Wnt/β-catenin induced epithelial to mesenchymal transition and stem cells for therapy

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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Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

Cancers ◽

10.3390/cancers11081058 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1058 ◽

Cited By ~ 10

Author(s):

Gener ◽

Rafael ◽

Seras-Franzoso ◽

Perez ◽

Pindado ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Distant Metastases ◽

Metastatic Potential ◽

Phenotypic Change ◽

Primary Tumors ◽

Mesenchymal Transition

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential.

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Abstract A039: The role of long noncoding RNAs in epithelial to mesenchymal transition and cancer stem cells

10.1158/1557-3125.advbc-a039 ◽

2013 ◽

Author(s):

Jason I. Herschkowitz ◽

Cristian Coarfa ◽

Aleix Prat ◽

Michael J. Toneff ◽

Katherine A. Hoadley ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Mesenchymal Transition

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The microRNA-200 family: still much to discover

BioMolecular Concepts ◽

10.1515/bmc-2016-0020 ◽

2016 ◽

Vol 7 (5-6) ◽

pp. 311-319 ◽

Cited By ~ 34

Author(s):

Daniel Senfter ◽

Sibylle Madlener ◽

Georg Krupitza ◽

Robert M. Mader

Keyword(s):

Cancer Progression ◽

Epithelial To Mesenchymal Transition ◽

Potential Role ◽

Predictive Biomarker ◽

Mesenchymal Transition ◽

Cellular Processes ◽

Active Regulation ◽

The Individual ◽

Open Issues

AbstractIn the last decade, microRNAs (miRs or miRNAs) became of great interest in cancer research due to their multifunctional and active regulation in a variety of vital cellular processes. In this review, we discuss the miR-200 family, which is composed of five members (miR-141, miR-200a/200b/200c and miR-429). Although being among the best investigated miRNAs in the field, there are still many open issues. Here, we describe the potential role of miR-200 as prognostic and/or predictive biomarker, its influence on motility and cell migration as well as its role in epithelial to mesenchymal transition (EMT) and metastasis formation in different tumour types. Recent studies also demonstrated the influence of miR-200 on drug resistance and described a correlation between miR-200 expression levels and overall survival of patients. Despite intense research in this field, the full role of the miR-200 family in cancer progression and metastasis is not completely understood and seems to differ between different tumour types and different cellular backgrounds. To elucidate these differences further, a finer characterisation of the role of the individual miRNA-200 family members is currently under investigation.

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Hypothesizing the potential role of melatonin in inhibiting epithelial to mesenchymal transition in oral squamous cell carcinoma

Medical Hypotheses ◽

10.1016/j.mehy.2020.110346 ◽

2020 ◽

Vol 145 ◽

pp. 110346

Author(s):

Thodur Madapusi Balaji ◽

Saranya Varadarajan ◽

Raghunathan Jagannathan ◽

A. Thirumal Raj ◽

Lakshmi Priya Sridhar ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epithelial To Mesenchymal Transition ◽

Potential Role ◽

Mesenchymal Transition

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Ovarian Cancer Recurrence: Role of Ovarian Stem Cells and Epithelial-to-Mesenchymal Transition

Journal of Cancer Science & Therapy ◽

10.4172/1948-5956.1000284 ◽

2014 ◽

Vol 06 (08) ◽

Cited By ~ 1

Author(s):

Damia G Guffanti F

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Cancer Recurrence ◽

Mesenchymal Transition ◽

Ovarian Stem Cells

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PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells

eLife ◽

10.7554/elife.14470 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 30

Author(s):

María Inés Pérez Millán ◽

Michelle L Brinkmeier ◽

Amanda H Mortensen ◽

Sally A Camper

Keyword(s):

Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Epithelial Mesenchymal Transition ◽

Stem Cell Differentiation ◽

Mouse Cell ◽

Mesenchymal Transition ◽

Genome Wide ◽

Transcription Factor Genes ◽

Therapeutic Perspective

Mutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the repression and activation of the pituitary transcription factor genes Hesx1 and Pou1f1, respectively. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome-wide analysis of PROP1 DNA binding and effects on gene expression in mutant mice, mouse isolated stem cells and engineered mouse cell lines. We determined that PROP1 is essential for stimulating stem cells to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to genes expressed in epithelial cells like Claudin 23, and to EMT inducer genes like Zeb2, Notch2 and Gli2. Zeb2 activation appears to be a key step in the EMT process. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation.

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Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases

Journal of Biomedical Science ◽

10.1186/s12929-021-00737-3 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Dongha Kim ◽

Keun Il Kim ◽

Sung Hee Baek

Keyword(s):

Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Regulation Of Gene Expression ◽

Cancer Microenvironment ◽

Mesenchymal Transition ◽

Physiological Processes ◽

Lysine Specific Demethylase ◽

Histone H3k4 ◽

Cerebral Physiology

AbstractLysine-specific demethylase 1 (LSD1) targets mono- or di-methylated histone H3K4 and H3K9 as well as non-histone substrates and functions in the regulation of gene expression as a transcriptional repressor or activator. This enzyme plays a pivotal role in various physiological processes, including development, differentiation, inflammation, thermogenesis, neuronal and cerebral physiology, and the maintenance of stemness in stem cells. LSD1 also participates in pathological processes, including cancer as the most representative disease. It promotes oncogenesis by facilitating the survival of cancer cells and by generating a pro-cancer microenvironment. In this review, we discuss the role of LSD1 in several aspects of cancer, such as hypoxia, epithelial-to-mesenchymal transition, stemness versus differentiation of cancer stem cells, as well as anti-tumor immunity. Additionally, the current understanding of the involvement of LSD1 in various other pathological processes is discussed.

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