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Cellular and Molecular Biology of Cancer Stem Cells

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (10 October 2023) | Viewed by 38685

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Special Issue Editors

Dr. Célia Maria Freitas Gomes

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Guest Editor

Center of Investigation in Environment, Genetics and Oncobiology, University of Coimbra, Coimbra, Portugal
Interests: cancer stem cells; drug resistance; self-renewal pathways; metastasis; theranostics; exosomes; solid tumors
Special Issues, Collections and Topics in MDPI journals

Dr. Sara R. Martins-Neves

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Guest Editor

Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR) - Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Interests: cancer stem cells; bone sarcomas; solid tumors; cancer chemoresistance; scientific communication
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cellular and molecular heterogeneity is a well-recognized feature of cancer. In fact, phenotypic plasticity contributing to that heterogeneity was recently coined as a new hallmark of cancer, which is conveyed by cancer stem cells (CSCs). CSCs are capable of generating diverse cell progeny that feed the tumor mass, and simultaneously are the culprits behind cancer evasion from the deleterious effects of chemo and/or radiation therapy, explaining the almost inevitable recurrence of several tumors. New insights into stem cell biology make the CSC concept more realistic, and understanding how tumor cells acquire these features has inspired the development of innovative strategies aiming to eradicate CSCs.

In this Special Issue of IJMS, “Cellular and Molecular Biology of Cancer Stem Cells”, we welcome original contributions and review articles that focus on:

Molecular and cellular mechanisms governing CSCs biology, namely: self-renewal signaling pathways, metabolic plasticity and cell cycle regulation;
Molecular drivers and mechanisms underlying CSCs therapy resistance and metastatic dissemination;
Microenvironmental regulators of cancer cell plasticity and mutual interconversion between cancer stem and non-stem cancer cells;
Emerging strategies of drug repurposing or repositioning and their effects on the behavior of CSCs, as well as strategies to therapeutically target CSC while sparing normal stem cells.

Dr. Célia Maria Freitas Gomes
Dr. Sara R. Martins-Neves
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cancer stem cells
self-renewal signaling
metabolic regulation
cell cycle regulation
cancer cell plasticity
phenotypic switching
resistance to therapy
targeted therapies
drug repurposing

Published Papers (13 papers)

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Research

Jump to: Review

23 pages, 4336 KiB

Open AccessArticle

Bioinformatics Analysis of RNA-seq Data Reveals Genes Related to Cancer Stem Cells in Colorectal Cancerogenesis

by Kristian Urh, Nina Zidar and Emanuela Boštjančič

Int. J. Mol. Sci. 2022, 23(21), 13252; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113252 - 31 Oct 2022

Cited by 3 | Viewed by 2343

Abstract

Cancer stem cells (CSC) play one of the crucial roles in the pathogenesis of various cancers, including colorectal cancer (CRC). Although great efforts have been made regarding our understanding of the cancerogenesis of CRC, CSC involvement in CRC development is still poorly understood. Using bioinformatics and RNA-seq data of normal mucosa, colorectal adenoma, and carcinoma (n = 106) from GEO and TCGA, we identified candidate CSC genes and analyzed pathway enrichment analysis (PEI) and protein–protein interaction analysis (PPI). Identified CSC-related genes were validated using qPCR and tissue samples from 47 patients with adenoma, adenoma with early carcinoma, and carcinoma without and with lymph node metastasis and were compared to normal mucosa. Six CSC-related genes were identified: ANLN, CDK1, ECT2, PDGFD, TNC, and TNXB. ANLN, CDK1, ECT2, and TNC were differentially expressed between adenoma and adenoma with early carcinoma. TNC was differentially expressed in CRC without lymph node metastases whereas ANLN, CDK1, and PDGFD were differentially expressed in CRC with lymph node metastases compared to normal mucosa. ANLN and PDGFD were differentially expressed between carcinoma without and with lymph node metastasis. Our study identified and validated CSC-related genes that might be involved in early stages of CRC development (ANLN, CDK1, ECT2, TNC) and in development of metastasis (ANLN, PDGFD). Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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17 pages, 4700 KiB

Open AccessArticle

Novel Thieno [2,3-b]pyridine Anticancer Compound Lowers Cancer Stem Cell Fraction Inducing Shift of Lipid to Glucose Metabolism

by Matij Pervan, Sandra Marijan, Anita Markotić, Lisa I. Pilkington, Natalie A. Haverkate, David Barker, Jóhannes Reynisson, Luka Meić, Mila Radan and Vedrana Čikeš Čulić

Int. J. Mol. Sci. 2022, 23(19), 11457; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911457 - 28 Sep 2022

Cited by 4 | Viewed by 2272

Abstract

Due to the role of cancer stem cells (CSCs) in tumor resistance and glycosphingolipid (GSL) involvement in tumor pathogenesis, we investigated the effect of a newly synthesized compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide 1 on the percentage of CSCs and the expression of six GSLs on CSCs and non-CSCs on breast cancer cell lines (MDA-MB-231 and MCF-7). We also investigated the effect of 1 on the metabolic profile of these cell lines. The MTT assay was used for cytotoxicity determination. Apoptosis and expression of GSLs were assessed by flow cytometry. A GC–MS-coupled system was used for the separation and identification of metabolites. Compound 1 was cytotoxic for both cell lines, and the majority of cells died by treatment-induced apoptosis. The percentage of CSCs was significantly lower in the MDA-MB-231 cell line. Treatment with 1 caused a decrease of CSC IV⁶Neu₅Ac-nLc₄Cer+ MDA-MB-231 cells. In the MCF-7 cell line, the percentage of GalNAc-GM1b+ CSCs was increased, while the expression of Gg₃Cer was decreased in both CSC and non-CSC. Twenty-one metabolites were identified by metabolic profiling. The major impact of the treatment was in glycolysis/gluconeogenesis, pyruvate and inositol metabolism. Compound 1 exhibited higher potency in MBA-MB-231 cells, and it deserves further examination. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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18 pages, 2881 KiB

Open AccessArticle

A Comprehensive Characterization of Stemness in Cell Lines and Primary Cells of Pancreatic Ductal Adenocarcinoma

by Benedetta Ferrara, Erica Dugnani, Valeria Sordi, Valentina Pasquale, Silvia Pellegrini, Michele Reni, Gianpaolo Balzano and Lorenzo Piemonti

Int. J. Mol. Sci. 2022, 23(18), 10663; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810663 - 14 Sep 2022

Cited by 4 | Viewed by 2111

Abstract

The aim of this study is to provide a comprehensive characterization of stemness in pancreatic ductal adenocarcinoma (PDAC) cell lines. Seventeen cell lines were evaluated for the expression of cancer stem cell (CSC) markers. The two putative pancreatic CSC phenotypes were expressed heterogeneously ranging from 0 to 99.35% (median 3.46) for ESA⁺CD24⁺CD44⁺ and 0 to 1.94% (median 0.13) for CXCR4⁺CD133⁺. Cell lines were classified according to ESA⁺CD24⁺CD44⁺ expression as: Low-Stemness (LS; <5%, n = 9, median 0.31%); Medium-Stemness (MS; 6–20%, n = 4, median 12.4%); and High-Stemness (HS; >20%, n = 4, median 95.8%) cell lines. Higher degree of stemness was associated with in vivo tumorigenicity but not with in vitro growth kinetics, clonogenicity, and chemo-resistance. A wide characterization (chemokine receptors, factors involved in pancreatic organogenesis, markers of epithelial–mesenchymal transition, and secretome) revealed that the degree of stemness was associated with KRT19 and NKX2.2 mRNA expression, with CD49a and CA19.9/Tie2 protein expression, and with the secretion of VEGF, IL-7, IL-12p70, IL-6, CCL3, IL-10, and CXCL9. The expression of stem cell markers was also evaluated on primary tumor cells from 55 PDAC patients who underwent pancreatectomy with radical intent, revealing that CXCR4⁺/CD133⁺ and CD24⁺ cells, but not ESA⁺CD24⁺CD44⁺, are independent predictors of mortality. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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13 pages, 2194 KiB

Open AccessArticle

Inhibition of the Phospholipase Cε–c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties

by Masashi Okada, Yurika Nakagawa-Saito, Yuta Mitobe, Asuka Sugai, Keita Togashi, Shuhei Suzuki and Chifumi Kitanaka

Int. J. Mol. Sci. 2022, 23(15), 8785; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158785 - 07 Aug 2022

Cited by 4 | Viewed by 1639

Abstract

Glioma stem cells (GSCs), the cancer stem cells of glioblastoma multiforme (GBM), contribute to the malignancy of GBM due to their resistance to therapy and tumorigenic potential; therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. The molecular mechanisms maintaining GSCs need to be elucidated in more detail for the development of GSC-targeted therapy. In comparison with patient-derived GSCs and their differentiated counterparts, we herein demonstrated for the first time that phospholipase C (PLC)ε was highly expressed in GSCs, in contrast to other PLC isoforms. A broad-spectrum PLC inhibitor suppressed the viability of GSCs, but not their stemness. Nevertheless, the knockdown of PLCε suppressed the survival of GSCs and induced cell death. The stem cell capacity of residual viable cells was also suppressed. Moreover, the survival of mice that were transplanted with PLCε knockdown-GSCs was longer than the control group. PLCε maintained the stemness of GSCs via the activation of JNK. The present study demonstrated for the first time that PLCε plays a critical role in maintaining the survival, stemness, and tumor initiation capacity of GSCs. Our study suggested that PLCε is a promising anti-GSC therapeutic target. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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12 pages, 3678 KiB

Open AccessArticle

HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny

by Yurika Nakagawa-Saito, Shinichi Saitoh, Yuta Mitobe, Asuka Sugai, Keita Togashi, Shuhei Suzuki, Chifumi Kitanaka and Masashi Okada

Int. J. Mol. Sci. 2022, 23(15), 8084; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158084 - 22 Jul 2022

Cited by 5 | Viewed by 2066

Abstract

Cancer stem cells (CSCs) are in general characterized by higher resistance to cell death and cancer therapies than non-stem differentiated cancer cells. However, we and others have recently revealed using glioma stem cells (GSCs) as a model that, unexpectedly, CSCs have specific vulnerabilities that make them more sensitive to certain drugs compared with their differentiated counterparts. We aimed in this study to discover novel drugs targeting such Achilles’ heels of GSCs as anti-GSC drug candidates to be used for the treatment of glioblastoma, the most therapy-resistant form of brain tumors. Here we report that domatinostat (4SC-202), a class I HDAC inhibitor, is one such candidate. At concentrations where it showed no or minimal growth inhibitory effect on differentiated GSCs and normal cells, domatinostat effectively inhibited the growth of GSCs mainly by inducing apoptosis. Furthermore, GSCs that survived domatinostat treatment lost their self-renewal capacity. These results suggested that domatinostat is a unique drug that selectively eliminates GSCs not only physically by inducing cell death but also functionally by inhibiting their self-renewal. Our findings also imply that class I HDACs and/or LSD1, another target of domatinostat, may possibly have a specific role in the maintenance of GSCs and therefore could be an attractive target in the development of anti-GSC therapies. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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Review

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28 pages, 2627 KiB

Open AccessReview

Self-Renewal and Pluripotency in Osteosarcoma Stem Cells’ Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers

by Sara R. Martins-Neves, Gabriela Sampaio-Ribeiro and Célia M. F. Gomes

Int. J. Mol. Sci. 2023, 24(9), 8401; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24098401 - 07 May 2023

Cited by 3 | Viewed by 3162

Abstract

Osteosarcoma is a highly malignant bone tumor derived from mesenchymal cells that contains self-renewing cancer stem cells (CSCs), which are responsible for tumor progression and chemotherapy resistance. Understanding the signaling pathways that regulate CSC self-renewal and survival is crucial for developing effective therapies. The Notch, Hedgehog, and Wnt/β-Catenin developmental pathways, which are essential for self-renewal and differentiation of normal stem cells, have been identified as important regulators of osteosarcoma CSCs and also in the resistance to anticancer therapies. Targeting these pathways and their interactions with embryonic markers and the tumor microenvironment may be a promising therapeutic strategy to overcome chemoresistance and improve the prognosis for osteosarcoma patients. This review focuses on the role of Notch, Hedgehog, and Wnt/β-Catenin signaling in regulating CSC self-renewal, pluripotency, and chemoresistance, and their potential as targets for anti-cancer therapies. We also discuss the relevance of embryonic markers, including SOX-2, Oct-4, NANOG, and KLF4, in osteosarcoma CSCs and their association with the aforementioned signaling pathways in overcoming drug resistance. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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16 pages, 707 KiB

Open AccessReview

Cellular and Molecular Biology of Cancer Stem Cells of Hepatocellular Carcinoma

by Kuo-Shyang Jeng, Chiung-Fang Chang, I-Shyang Sheen, Chi-Juei Jeng and Chih-Hsuan Wang

Int. J. Mol. Sci. 2023, 24(2), 1417; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021417 - 11 Jan 2023

Cited by 11 | Viewed by 3340

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death globally. The cancer stem cells (CSCs) of HCC are responsible for tumor growth, invasion, metastasis, recurrence, chemoresistance, target therapy resistance and radioresistance. The reported main surface markers used to identify liver CSCs include epithelial cell adhesion/activating molecule (EpCAM), cluster differentiation 90 (CD90), CD44 and CD133. The main molecular signaling pathways include the Wnt/β-catenin, transforming growth factors-β (TGF-β), sonic hedgehog (SHH), PI3K/Akt/mTOR and Notch. Patients with EpCAM-positive alpha-fetoprotein (AFP)-positive HCC are usually young but have advanced tumor-node-metastasis (TNM) stages. CD90-positive HCCs are usually poorly differentiated with worse prognosis. Those with CD44-positive HCC cells develop early metastases. Those with CD133 expression have a higher recurrence rate and a shorter overall survival. The Wnt/β-catenin signaling pathway triggers angiogenesis, tumor infiltration and metastasis through the enhancement of angiogenic factors. All CD133+ liver CSCs, CD133+/EpCAM+ liver CSCs and CD44+ liver CSCs contribute to sorafenib resistance. SHH signaling could protect HCC cells against ionizing radiation in an autocrine manner. Reducing the CSC population of HCC is crucial for the improvement of the therapy of advanced HCC. However, targeting CSCs of HCC is still challenging. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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17 pages, 1136 KiB

Open AccessReview

The Role of Tumor Microenvironment in Regulating the Plasticity of Osteosarcoma Cells

by Boren Tian, Xiaoyun Du, Shiyu Zheng and Yan Zhang

Int. J. Mol. Sci. 2022, 23(24), 16155; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232416155 - 18 Dec 2022

Cited by 7 | Viewed by 1420

Abstract

Osteosarcoma (OS) is a malignancy that is becoming increasingly common in adolescents. OS stem cells (OSCs) form a dynamic subset of OS cells that are responsible for malignant progression and chemoradiotherapy resistance. The unique properties of OSCs, including self-renewal, multilineage differentiation and metastatic potential, 149 depend closely on their tumor microenvironment. In recent years, the likelihood of its dynamic plasticity has been extensively studied. Importantly, the tumor microenvironment appears to act as the main regulatory component of OS cell plasticity. For these reasons aforementioned, novel strategies for OS treatment focusing on modulating OS cell plasticity and the possibility of modulating the composition of the tumor microenvironment are currently being explored. In this paper, we review recent studies describing the phenomenon of OSCs and factors known to influence phenotypic plasticity. The microenvironment, which can regulate OSC plasticity, has great potential for clinical exploitation and provides different perspectives for drug and treatment design for OS. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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28 pages, 2231 KiB

Open AccessReview

Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters

by Sara R. Martins-Neves, Gabriela Sampaio-Ribeiro and Célia M. F. Gomes

Int. J. Mol. Sci. 2022, 23(19), 11416; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911416 - 27 Sep 2022

Cited by 5 | Viewed by 2560

Abstract

Osteosarcoma is amongst the most prevalent bone sarcomas and majorly afflicts children and adolescents. Therapeutic regimens based on the triad of doxorubicin, cisplatin and methotrexate have been used as the state-of-the-art approach to clinical treatment and management, with no significant improvements in the general outcomes since their inception in the early 1970s. This fact raises the following problematic questions: Why do some patients still relapse despite an initial good response to therapy? Why do nearly 30% of patients not respond to neoadjuvant therapies? Does residual persistent disease contribute to relapses and possible metastatic dissemination? Accumulating evidence suggests that chemoresistant cancer stem cells may be the major culprits contributing to those challenging clinical outcomes. Herein, we revisit the maneuvers that cancer stem cells devise for eluding cell killing by the classic cytotoxic therapies used in osteosarcoma, highlighting studies that demonstrate the complex crosstalk of signaling pathways that cancer stem cells can recruit to become chemoresistant. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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16 pages, 1056 KiB

Open AccessReview

Flow Cytometric Identification of Hematopoietic and Leukemic Blast Cells for Tailored Clinical Follow-Up of Acute Myeloid Leukemia

by Vera Weeda, Stefan G. C. Mestrum and Math P. G. Leers

Int. J. Mol. Sci. 2022, 23(18), 10529; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810529 - 11 Sep 2022

Cited by 6 | Viewed by 5365

Abstract

Acute myeloid leukemia (AML) is a myeloid malignancy that is characterized by the accumulation of leukemic blast cells, which originate from hematopoietic stem cells that have undergone leukemic transformation and/or are more mature progenitors that have gained stemness features. Currently, no consensus exists for the flow cytometric identification of normal blast cells and their leukemic counterparts by their antigenic expression profile. Differentiating between the benign cells and the malignant cells is crucial for the further deployment of immunophenotype panels for the clinical follow-up of AML patients. This review provides an overview of immunophenotypic markers that allow the identification of leukemic blast cells in the bone marrow with multiparameter flow cytometry. This technique allows the identification of hematopoietic blast cells at the level of maturing cells by their antigen expression profile. While aberrant antigen expression of a single immunophenotypic marker cell cannot be utilized in order to differentiate leukemic blast cells from normal blast cells, combinations of multiple immunophenotypic markers can enable the distinction of normal and leukemic blast cells. The identification of these markers has provided new perspectives for tailored clinical follow-up, including therapy management, diagnostics, and prognostic purposes. The immunophenotypic marker panels, however, should be developed by carefully considering the variable antigen marker expression profile of individual patients. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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14 pages, 1358 KiB

Open AccessReview

Addiction of Cancer Stem Cells to MUC1-C in Triple-Negative Breast Cancer Progression

by Nami Yamashita and Donald Kufe

Int. J. Mol. Sci. 2022, 23(15), 8219; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158219 - 26 Jul 2022

Cited by 15 | Viewed by 3346

Abstract

Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options. TNBC progression is associated with expansion of cancer stem cells (CSCs). Few insights are available regarding druggable targets that drive the TNBC CSC state. This review summarizes the literature on TNBC CSCs and the compelling evidence that they are addicted to the MUC1-C transmembrane protein. In normal epithelia, MUC1-C is activated by loss of homeostasis and induces reversible wound-healing responses of inflammation and repair. However, in settings of chronic inflammation, MUC1-C promotes carcinogenesis. MUC1-C induces EMT, epigenetic reprogramming and chromatin remodeling in TNBC CSCs, which are dependent on MUC1-C for self-renewal and tumorigenicity. MUC1-C-induced lineage plasticity in TNBC CSCs confers DNA damage resistance and immune evasion by chronic activation of inflammatory pathways and global changes in chromatin architecture. Of therapeutic significance, an antibody generated against the MUC1-C extracellular domain has been advanced in a clinical trial of anti-MUC1-C CAR T cells and in IND-enabling studies for development as an antibody–drug conjugate (ADC). Agents targeting the MUC1-C cytoplasmic domain have also entered the clinic and are undergoing further development as candidates for advancing TNBC treatment. Eliminating TNBC CSCs will be necessary for curing this recalcitrant cancer and MUC1-C represents a promising druggable target for achieving that goal. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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18 pages, 721 KiB

Open AccessReview

Cancer Stem Cells and Their Possible Implications in Cervical Cancer: A Short Review

by Riccardo Di Fiore, Sherif Suleiman, Rosa Drago-Ferrante, Yashwanth Subbannayya, Francesca Pentimalli, Antonio Giordano and Jean Calleja-Agius

Int. J. Mol. Sci. 2022, 23(9), 5167; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095167 - 05 May 2022

Cited by 22 | Viewed by 4298

Abstract

Cervical cancer (CC) is the fourth most common type of gynecological malignancy affecting females worldwide. Most CC cases are linked to infection with high-risk human papillomaviruses (HPV). There has been a significant decrease in the incidence and death rate of CC due to effective cervical Pap smear screening and administration of vaccines. However, this is not equally available throughout different societies. The prognosis of patients with advanced or recurrent CC is particularly poor, with a one-year relative survival rate of a maximum of 20%. Increasing evidence suggests that cancer stem cells (CSCs) may play an important role in CC tumorigenesis, metastasis, relapse, and chemo/radio-resistance, thus representing potential targets for a better therapeutic outcome. CSCs are a small subpopulation of tumor cells with self-renewing ability, which can differentiate into heterogeneous tumor cell types, thus creating a progeny of cells constituting the bulk of tumors. Since cervical CSCs (CCSC) are difficult to identify, this has led to the search for different markers (e.g., ABCG2, ITGA6 (CD49f), PROM1 (CD133), KRT17 (CK17), MSI1, POU5F1 (OCT4), and SOX2). Promising therapeutic strategies targeting CSC-signaling pathways and the CSC niche are currently under development. Here, we provide an overview of CC and CCSCs, describing the phenotypes of CCSCs and the potential of targeting CCSCs in the management of CC. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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21 pages, 4658 KiB

Open AccessReview

Tumour Stem Cells in Breast Cancer

by Marina Ibragimova, Matvey Tsyganov and Nikolai Litviakov

Int. J. Mol. Sci. 2022, 23(9), 5058; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095058 - 02 May 2022

Cited by 14 | Viewed by 3075

Abstract

Tumour stem cells (CSCs) are a self-renewing population that plays important roles in tumour initiation, recurrence, and metastasis. Although the medical literature is extensive, problems with CSC identification and cancer therapy remain. This review provides the main mechanisms of CSC action in breast cancer (BC): CSC markers and signalling pathways, heterogeneity, plasticity, and ecological behaviour. The dynamic heterogeneity of CSCs and the dynamic transitions of CSC⁻ non-CSCs and their significance for metastasis are considered. Full article

(This article belongs to the Special Issue Cellular and Molecular Biology of Cancer Stem Cells)

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