scholarly journals Cancer Stem Cells and Nucleolin as Drivers of Carcinogenesis

2021 ◽  
Vol 14 (1) ◽  
pp. 60
Author(s):  
Laura Sofia Carvalho ◽  
Nélio Gonçalves ◽  
Nuno André Fonseca ◽  
João Nuno Moreira
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Clonal Evolution ◽  
Therapy Resistance ◽  
Cellular Heterogeneity ◽  
Multifunctional Protein ◽  
Mesenchymal Transition ◽  
Cancer Hallmarks

Cancer, one of the most mortal diseases worldwide, is characterized by the gain of specific features and cellular heterogeneity. Clonal evolution is an established theory to explain heterogeneity, but the discovery of cancer stem cells expanded the concept to include the hierarchical growth and plasticity of cancer cells. The activation of epithelial-to-mesenchymal transition and its molecular players are widely correlated with the presence of cancer stem cells in tumors. Moreover, the acquisition of certain oncological features may be partially attributed to alterations in the levels, location or function of nucleolin, a multifunctional protein involved in several cellular processes. This review aims at integrating the established hallmarks of cancer with the plasticity of cancer cells as an emerging hallmark; responsible for tumor heterogeneity; therapy resistance and relapse. The discussion will contextualize the involvement of nucleolin in the establishment of cancer hallmarks and its application as a marker protein for targeted anticancer therapies

scholarly journals Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating–cancer stem cells: distinct, overlapping or same populations

Oncogene ◽  
2011 ◽  
Vol 30 (46) ◽  
pp. 4609-4621 ◽  
Author(s):  
S Floor ◽  
W C G van Staveren ◽  
D Larsimont ◽  
J E Dumont ◽  
C Maenhaut
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Chronic Oxidative Stress Promotes Molecular Changes Associated with Epithelial Mesenchymal Transition, NRF2, and Breast Cancer Stem Cell Phenotype

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 633 ◽  
Author(s):  
Ana Čipak Gašparović ◽  
Lidija Milković ◽  
Nadia Dandachi ◽  
Stefanie Stanzer ◽  
Iskra Pezdirc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapy Resistance ◽  
Mesenchymal Transition ◽  
Chronic Oxidative Stress ◽  
Emt Markers

Oxidative stress plays a role in carcinogenesis, but it also contributes to the modulation of tumor cells and microenvironment caused by chemotherapeutics. One of the consequences of oxidative stress is lipid peroxidation, which can, through reactive aldehydes such as 4-hydroxy-2-nonenal (HNE), affect cell signaling pathways. On the other hand, cancer stem cells (CSC) are now recognized as a major factor of malignancy by causing metastasis, relapse, and therapy resistance. Here, we evaluated whether oxidative stress and HNE modulation of the microenvironment can influence CSC growth, modifications of the epithelial to mesenchymal transition (EMT) markers, the antioxidant system, and the frequency of breast cancer stem cells (BCSC). Our results showed that oxidative changes in the microenvironment of BCSC and particularly chronic oxidative stress caused changes in the proliferation and growth of breast cancer cells. In addition, changes associated with EMT, increase in glutathione (GSH) and Nuclear factor erythroid 2-related factor 2 (NRF2) were observed in breast cancer cells grown on HNE pretreated collagen and under chronic oxidative stress. Our results suggest that chronic oxidative stress can be a bidirectional modulator of BCSC fate. Low levels of HNE can increase differentiation markers in BCSC, while higher levels increased GSH and NRF2 as well as certain EMT markers, thereby increasing therapy resistance.

scholarly journals Tackling Cancer Stem Cells via Inhibition of EMT Transcription Factors

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Megan Mladinich ◽  
Diane Ruan ◽  
Chia-Hsin Chan
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Ample Evidence ◽  
Mesenchymal Transition ◽  
Secondary Tumors ◽  
Patient Prognosis

Cancer stem cell (CSC) has become recognized for its role in both tumorigenesis and poor patient prognosis in recent years. Traditional therapeutics are unable to effectively eliminate this group of cells from the bulk population of cancer cells, allowing CSCs to persist posttreatment and thus propagate into secondary tumors. The therapeutic potential of eliminating CSCs, to decrease tumor relapse, has created a demand for identifying mechanisms that directly target and eliminate cancer stem cells. Molecular profiling has shown that cancer cells and tumors that exhibit the CSC phenotype also express genes associated with the epithelial-to-mesenchymal transition (EMT) feature. Ample evidence has demonstrated that upregulation of master transcription factors (TFs) accounting for the EMT process such as Snail/Slug and Twist can reprogram cancer cells from differentiated to stem-like status. Despite being appealing therapeutic targets for tackling CSCs, pharmacological approaches that directly target EMT-TFs remain impossible. In this review, we will summarize recent advances in the regulation of Snail/Slug and Twist at transcriptional, translational, and posttranslational levels and discuss the clinical implication and application for EMT blockade as a promising strategy for CSC targeting.

scholarly journals Androgen receptor and prostate cancer stem cells: biological mechanisms and clinical implications

2015 ◽  
Vol 22 (6) ◽  
pp. T209-T220 ◽  
Author(s):  
Qu Deng ◽  
Dean G Tang
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Androgen Receptor ◽  
Cancer Stem Cells ◽  
Clonal Evolution ◽  
Population Level ◽  
Cell Types ◽  
Therapy Resistance ◽  
Cellular Heterogeneity ◽  
Prostate Cancer Stem Cells

Prostate cancer (PCa) contains phenotypically and functionally distinct cells, and this cellular heterogeneity poses clinical challenges as the distinct cell types likely respond differently to various therapies. Clonal evolution, driven by genetic instability, and intraclonal cancer cell diversification, driven by cancer stem cells (CSCs), together create tumor cell heterogeneity. In this review, we first discuss PCa stem cells (PCSCs) and heterogeneity of androgen receptor (AR) expression in primary, metastatic, and treatment-failed PCa. Based on literature reports and our own studies, we hypothesize that, whereas PCSCs in primary and untreated tumors and models are mainly AR−, PCSCs in CRPCs could be either AR+or AR−/lo. We illustrate the potential mechanisms AR+and AR−PCSCs may employ to propagate PCa at the population level, mediate therapy resistance, and metastasize. As a result, targeting AR alone may not achieve long-lasting therapeutic efficacy. Elucidating the roles of AR and PCSCs should provide important clues to designing novel personalized combinatorial therapeutic protocols targeting both AR+and AR−PCa cells.

scholarly journals MiRNA-mediated EMT and CSCs in cancer chemoresistance

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Bing Dong ◽  
Shiyu Li ◽  
Shuangli Zhu ◽  
Ming Yi ◽  
Suxia Luo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Complex Process ◽  
Cancer Chemoresistance

AbstractCancer stem cells (CSCs) are a small group of cancer cells, which contribute to tumorigenesis and cancer progression. Cancer cells undergoing epithelial-to-mesenchymal transition (EMT) acquire the chemoresistant ability, which is regarded as an important feature of CSCs. Thus, there emerges an opinion that the generation of CSCs is considered to be driven by EMT. In this complex process, microRNAs (miRNAs) are found to play a key role. In order to overcome the drug resistance, inhibiting EMT as well as CSCs phenotype seem feasible. Thereinto, regulating the EMT- or CSCs-associated miRNAs is a crucial approach. Herein, we conduct this review to elaborate on the complicated interplay between EMT and CSCs in cancer chemoresistance, which is modulated by miRNAs. In addition, we elucidate the therapeutic strategy to overcome drug resistance through targeting EMT and CSCs.

scholarly journals EMT and Stemness—Key Players in Pancreatic Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1136 ◽  
Author(s):  
Eva Rodriguez-Aznar ◽  
Lisa Wiesmüller ◽  
Bruno Sainz ◽  
Patrick C. Hermann
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Progression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Developmental Process ◽  
Therapy Resistance ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition

Metastasis and tumor progression are the major cause of death in patients suffering from pancreatic ductal adenocarcinoma. Tumor growth and especially dissemination are typically associated with activation of an epithelial-to-mesenchymal transition (EMT) program. This phenotypic transition from an epithelial to a mesenchymal state promotes migration and survival both during development and in cancer progression. When re-activated in pathological contexts such as cancer, this type of developmental process confers additional stemness properties to specific subsets of cells. Cancer stem cells (CSCs) are a subpopulation of cancer cells with stem-like features that are responsible for the propagation of the tumor as well as therapy resistance and cancer relapse, but also for circulating tumor cell release and metastasis. In support of this concept, EMT transcription factors generate cells with stem cell properties and mediate chemoresistance. However, their role in pancreatic ductal adenocarcinoma metastasis remains controversial. As such, a better characterization of CSC populations will be crucial in future development of therapies targeting these cells. In this review, we will discuss the latest updates on the mechanisms common to pancreas development and CSC-mediated tumor progression.

scholarly journals Role of Claudin Proteins in Regulating Cancer Stem Cells and Chemoresistance-Potential Implication in Disease Prognosis and Therapy

2019 ◽  
Vol 21 (1) ◽  
pp. 53 ◽  
Author(s):  
Saiprasad Gowrikumar ◽  
Amar B. Singh ◽  
Punita Dhawan
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Therapy Resistance ◽  
Cell Phenotype ◽  
Potential Implication ◽  
Mesenchymal Transition ◽  
Cell Cell

Claudins are cell–cell adhesion proteins, which are expressed in tight junctions (TJs), the most common apical cell-cell adhesion. Claudin proteins help to regulate defense and barrier functions, as well as differentiation and polarity in epithelial and endothelial cells. A series of studies have now reported dysregulation of claudin proteins in cancers. However, the precise mechanisms are still not well understood. Nonetheless, studies have clearly demonstrated a causal role of multiple claudins in the regulation of epithelial to mesenchymal transition (EMT), a key feature in the acquisition of a cancer stem cell phenotype in cancer cells. In addition, claudin proteins are known to modulate therapy resistance in cancer cells, a feature associated with cancer stem cells. In this review, we have focused primarily on highlighting the causal link between claudins, cancer stem cells, and therapy resistance. We have also contemplated the significance of claudins as novel targets in improving the efficacy of cancer therapy. Overall, this review provides a much-needed understanding of the emerging role of claudin proteins in cancer malignancy and therapeutic management.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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.

Sign in / Sign up

Export Citation Format

Share Document