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Special Issue "New Advance on Cancer Stem Cells"

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

Deadline for manuscript submissions: 31 August 2023 | Viewed by 3878

Special Issue Editor

School of Bioscience and Biotechnology, Tokyo University of Technology, 1401-1 Katakura-Machi, Hachioji 192-0982, Tokyo, Japan
Interests: cancer stem cell; artificial intelligence; RNAi screening; programed cell death; reactive oxygene species; mitochondrial membrane potential

Special Issue Information

Dear Colleagues,

A concept of cancer stem cells (CSCs) was introduced for the first time by Weissman IL in 2001 to consider rare cells with self-renewal potential that initiate tumorigenesis. It has been proven by many studies focusing on blood, breast, lung, liver, colon, stomach, and brain tumors, and melanoma. In recent years, the original concept has been reconstructed by considering plasticity of cell between differentiated and undifferentiated cells. The tumor microenvironment can stimulate differentiated tumor cells to acquire cancer stem cell characteristics. CSCs can originate not only from normal stem cells but also cancer cells. Although knowledge regarding the biology of CSCs is accumulating, it is not sufficient, with several gaps in topics such as the cell cycle, gene expression, cell senescence, niche, morphology, and sensitivity to therapeutics. Thus, more knowledge is required which can lead to the development of new diagnosis of CSCs and therapy targeting CSCs. This Special Issue aims to contribute to CSC research for cancer therapy. All research on CSC biology is welcome. This includes not only basic CSC biomarkers, cancer-associated fibroblast, CSC signaling, medicine including drugs, antibody, nucleic acid, and cell therapy and diagnosis, but also methods incorporating artificial intelligence technology. Through this issue, we hope to help scientists toward the development of CSC-based cancer therapy and diagnosis.

Dr. Tomoyasu Sugiyama
Guest Editor

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 cell
  • biomarker
  • signaling
  • cancer-associated fibroblast
  • artificial intelligence
  • cell therapy
  • antibody therapy
  • cell therapy
  • gene expression

Published Papers (5 papers)

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Research

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Article
Oncogenic Impact of TONSL, a Homologous Recombination Repair Protein at the Replication Fork, in Cancer Stem Cells
Int. J. Mol. Sci. 2023, 24(11), 9530; https://doi.org/10.3390/ijms24119530 - 31 May 2023
Viewed by 315
Abstract
We investigated the role of TONSL, a mediator of homologous recombination repair (HRR), in stalled replication fork double-strand breaks (DSBs) in cancer. Publicly available clinical data (tumors from the ovary, breast, stomach and lung) were analyzed through KM Plotter, cBioPortal and Qomics. Cancer [...] Read more.
We investigated the role of TONSL, a mediator of homologous recombination repair (HRR), in stalled replication fork double-strand breaks (DSBs) in cancer. Publicly available clinical data (tumors from the ovary, breast, stomach and lung) were analyzed through KM Plotter, cBioPortal and Qomics. Cancer stem cell (CSC)-enriched cultures and bulk/general mixed cell cultures (BCCs) with RNAi were employed to determine the effect of TONSL loss in cancer cell lines from the ovary, breast, stomach, lung, colon and brain. Limited dilution assays and ALDH assays were used to quantify the loss of CSCs. Western blotting and cell-based homologous recombination assays were used to identify DNA damage derived from TONSL loss. TONSL was expressed at higher levels in cancer tissues than in normal tissues, and higher expression was an unfavorable prognostic marker for lung, stomach, breast and ovarian cancers. Higher expression of TONSL is partly associated with the coamplification of TONSL and MYC, suggesting its oncogenic role. The suppression of TONSL using RNAi revealed that it is required in the survival of CSCs in cancer cells, while BCCs could frequently survive without TONSL. TONSL dependency occurs through accumulated DNA damage-induced senescence and apoptosis in TONSL-suppressed CSCs. The expression of several other major mediators of HRR was also associated with worse prognosis, whereas the expression of error-prone nonhomologous end joining molecules was associated with better survival in lung adenocarcinoma. Collectively, these results suggest that TONSL-mediated HRR at the replication fork is critical for CSC survival; targeting TONSL may lead to the effective eradication of CSCs. Full article
(This article belongs to the Special Issue New Advance on Cancer Stem Cells)
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Article
Deep Learning of Phase-Contrast Images of Cancer Stem Cells Using a Selected Dataset of High Accuracy Value Using Conditional Generative Adversarial Networks
Int. J. Mol. Sci. 2023, 24(6), 5323; https://doi.org/10.3390/ijms24065323 - 10 Mar 2023
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Abstract
Artificial intelligence (AI) technology for image recognition has the potential to identify cancer stem cells (CSCs) in cultures and tissues. CSCs play an important role in the development and relapse of tumors. Although the characteristics of CSCs have been extensively studied, their morphological [...] Read more.
Artificial intelligence (AI) technology for image recognition has the potential to identify cancer stem cells (CSCs) in cultures and tissues. CSCs play an important role in the development and relapse of tumors. Although the characteristics of CSCs have been extensively studied, their morphological features remain elusive. The attempt to obtain an AI model identifying CSCs in culture showed the importance of images from spatially and temporally grown cultures of CSCs for deep learning to improve accuracy, but was insufficient. This study aimed to identify a process that is significantly efficient in increasing the accuracy values of the AI model output for predicting CSCs from phase-contrast images. An AI model of conditional generative adversarial network (CGAN) image translation for CSC identification predicted CSCs with various accuracy levels, and convolutional neural network classification of CSC phase-contrast images showed variation in the images. The accuracy of the AI model of CGAN image translation was increased by the AI model built by deep learning of selected CSC images with high accuracy previously calculated by another AI model. The workflow of building an AI model based on CGAN image translation could be useful for the AI prediction of CSCs. Full article
(This article belongs to the Special Issue New Advance on Cancer Stem Cells)
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Review

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Review
Stearoyl-CoA Desaturase 1 as a Therapeutic Biomarker: Focusing on Cancer Stem Cells
Int. J. Mol. Sci. 2023, 24(10), 8951; https://doi.org/10.3390/ijms24108951 - 18 May 2023
Viewed by 316
Abstract
The dysregulation of lipid metabolism and alterations in the ratio of monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) have been implicated in cancer progression and stemness. Stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in lipid desaturation, is crucial in regulating this [...] Read more.
The dysregulation of lipid metabolism and alterations in the ratio of monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) have been implicated in cancer progression and stemness. Stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in lipid desaturation, is crucial in regulating this ratio and has been identified as an important regulator of cancer cell survival and progression. SCD1 converts SFAs into MUFAs and is important for maintaining membrane fluidity, cellular signaling, and gene expression. Many malignancies, including cancer stem cells, have been reported to exhibit high expression of SCD1. Therefore, targeting SCD1 may provide a novel therapeutic strategy for cancer treatment. In addition, the involvement of SCD1 in cancer stem cells has been observed in various types of cancer. Some natural products have the potential to inhibit SCD1 expression/activity, thereby suppressing cancer cell survival and self-renewal activity. Full article
(This article belongs to the Special Issue New Advance on Cancer Stem Cells)
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Review
Cell Therapy as Target Therapy against Colon Cancer Stem Cells
Int. J. Mol. Sci. 2023, 24(9), 8163; https://doi.org/10.3390/ijms24098163 - 03 May 2023
Viewed by 686
Abstract
Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with properties, such as self-renewal, differentiation, and tumorigenicity. CSCs have been proposed as a plausible therapeutic target as they are responsible for tumor recurrence, metastasis, and conventional therapy resistance. Selectively targeting [...] Read more.
Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with properties, such as self-renewal, differentiation, and tumorigenicity. CSCs have been proposed as a plausible therapeutic target as they are responsible for tumor recurrence, metastasis, and conventional therapy resistance. Selectively targeting CSCs is a promising strategy to eliminate the propagation of tumor cells and impair overall tumor development. Recent research shows that several immune cells play a crucial role in regulating tumor cell proliferation by regulating different CSC maintenance or proliferation pathways. There have been great advances in cellular immunotherapy using T cells, natural killer (NK) cells, macrophages, or stem cells for the selective targeting of tumor cells or CSCs in colorectal cancer (CRC). This review summarizes the CRC molecular profiles that may benefit from said therapy and the main vehicles used in cell therapy against CSCs. We also discuss the challenges, limitations, and advantages of combining conventional and/or current targeted treatments in the late stages of CRC. Full article
(This article belongs to the Special Issue New Advance on Cancer Stem Cells)
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Review
Bromodomain (BrD) Family Members as Regulators of Cancer Stemness—A Comprehensive Review
Int. J. Mol. Sci. 2023, 24(2), 995; https://doi.org/10.3390/ijms24020995 - 04 Jan 2023
Viewed by 1042
Abstract
Epigenetic mechanisms involving DNA methylation and chromatin modifications have emerged as critical facilitators of cancer heterogeneity, substantially affecting cancer development and progression, modulating cell phenotypes, and enhancing or inhibiting cancer cell malignant properties. Not surprisingly, considering the importance of epigenetic regulators in normal [...] Read more.
Epigenetic mechanisms involving DNA methylation and chromatin modifications have emerged as critical facilitators of cancer heterogeneity, substantially affecting cancer development and progression, modulating cell phenotypes, and enhancing or inhibiting cancer cell malignant properties. Not surprisingly, considering the importance of epigenetic regulators in normal stem cell maintenance, many chromatin-related proteins are essential to maintaining the cancer stem cell (CSC)-like state. With increased tumor-initiating capacities and self-renewal potential, CSCs promote tumor growth, provide therapy resistance, spread tumors, and facilitate tumor relapse after treatment. In this review, we characterized the epigenetic mechanisms that regulate the acquisition and maintenance of cancer stemness concerning selected epigenetic factors belonging to the Bromodomain (BrD) family of proteins. An increasing number of BrD proteins reinforce cancer stemness, supporting the maintenance of the cancer stem cell population in vitro and in vivo via the utilization of distinct mechanisms. As bromodomain possesses high druggable potential, specific BrD proteins might become novel therapeutic targets in cancers exhibiting de-differentiated tumor characteristics. Full article
(This article belongs to the Special Issue New Advance on Cancer Stem Cells)
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