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Special Issue "New Advance on 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 Oncology".

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

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Special Issue Editor

Dr. Tomoyasu Sugiyama

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Guest 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

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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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Open AccessArticle

Oncogenic Impact of TONSL, a Homologous Recombination Repair Protein at the Replication Fork, in Cancer Stem Cells

and

Int. J. Mol. Sci. 2023, 24(11), 9530; https://doi.org/10.3390/ijms24119530 - 31 May 2023

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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 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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Open AccessArticle

Deep Learning of Phase-Contrast Images of Cancer Stem Cells Using a Selected Dataset of High Accuracy Value Using Conditional Generative Adversarial Networks

and

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 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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Open AccessReview

Stearoyl-CoA Desaturase 1 as a Therapeutic Biomarker: Focusing on Cancer Stem Cells

Jin-Young Min

and

Do-Hee Kim

Int. J. Mol. Sci. 2023, 24(10), 8951; https://doi.org/10.3390/ijms24108951 - 18 May 2023

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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 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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Open AccessReview

Cell Therapy as Target Therapy against Colon Cancer Stem Cells

Elsa N. Garza Treviño

Adriana G. Quiroz Reyes

Juan Antonio Rojas Murillo

David A de la Garza Kalife

Paulina Delgado Gonzalez

Jose F. Islas

Ana Esther Estrada Rodriguez

and

Carlos A. Gonzalez Villarreal

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 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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Open AccessReview

Bromodomain (BrD) Family Members as Regulators of Cancer Stemness—A Comprehensive Review

Patrycja Czerwinska

and

Andrzej Adam Mackiewicz

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 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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