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Molecular Aspects of Cancer Stem Cell Biology and Their Therapeutic Implications

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 March 2026 | Viewed by 743

Special Issue Editor


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Guest Editor
Laboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia
Interests: cancer; toll-like receptors; DAMPs; tumor microenvironment; cancer stem cells; radiotherapy

Special Issue Information

Dear Colleagues,

Cancer stem cells (CSCs) are an aggressive subpopulation of cancer cells, characterized by the unique ability to self-renew and their great plasticity, which allows them to differentiate into various cell types as well as dedifferentiate. This subpopulation also has high metastatic potential and is characterized by high expression levels of efflux pumps and therapy resistance. Standard treatments often fail to eliminate cancer stem cells, leading to significant interest in developing therapies that specifically target this subpopulation.

In this Special Issue entitled ‘Molecular Aspects of Cancer Stem Cell Biology and Their Therapeutic Implications’, we encourage the submission of original research papers and reviews regarding the novel insights into CSC biology and recent advances in their therapy. We will focus on the molecular basis of the CSCs, with emphasis on key signaling pathways, stemness-related transcription factors, stemness markers, and mechanisms of therapy resistance.

Suitable topics include, but are not limited to, the following:

  • Cancer stem cell biology and plasticity.
  • Crosstalk between cancer stem cells and tumor microenvironment.
  • Therapy resistance
  • Novel therapies targeting cancer stem cells.

Dr. Tanja Matijevic Glavan
Guest Editor

Manuscript Submission Information

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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
  • chemotherapy
  • radiotherapy
  • transcription factors
  • stemness properties
  • chemoresistance
  • radioresistance

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Published Papers (1 paper)

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Research

23 pages, 4080 KB  
Article
Contrasting Impacts of Targeted Disruption of the Cancer Stem Cell Marker CD133 and Its Epigenetic Regulator TRIM28 in Colorectal Cancer Cells
by Irina V. Kholodenko, Aleena A. Saidova, Daria M. Potashnikova, Viktoriia A. Arzumanian, Daniil D. Romashin, Anna V. Tvorogova, Ekaterina V. Poverennaya, Konstantin N. Yarygin and Yan S. Kim
Int. J. Mol. Sci. 2025, 26(22), 10862; https://doi.org/10.3390/ijms262210862 - 9 Nov 2025
Viewed by 638
Abstract
Cancer stem cells (CSCs) play a crucial role in colorectal cancer by sustaining intratumoral heterogeneity, therapeutic resistance, and metastatic potential. CD133 (PROM1) is among the most frequently used surface markers for CSC identification, whereas TRIM28, a versatile epigenetic regulator, has been implicated in [...] Read more.
Cancer stem cells (CSCs) play a crucial role in colorectal cancer by sustaining intratumoral heterogeneity, therapeutic resistance, and metastatic potential. CD133 (PROM1) is among the most frequently used surface markers for CSC identification, whereas TRIM28, a versatile epigenetic regulator, has been implicated in controlling CD133 expression and stem-like features. In this study, we performed a detailed molecular and functional analysis of Caco2 colorectal cancer cell clones with individual knockouts of CD133 or TRIM28. Elimination of CD133 neither altered global gene expression, as confirmed by transcriptome profiling, nor affected key cellular properties. In contrast, loss of TRIM28 led to a marked reduction in CD133 protein abundance and induced extensive molecular and phenotypic remodeling. TRIM28 knockout was associated with broad transcriptomic changes involving more than 500 differentially expressed genes, decreased proliferative activity monitored by time-lapse imaging, and reduced sensitivity to paclitaxel, cisplatin, and curcumin. Furthermore, immune evasion molecules CD24 and CD47 (“don’t eat me” signals) were strongly upregulated in TRIM28-deficient cells, consistently confirmed by both RNA-Seq and flow cytometry analyses. At the same time, imaging flow cytometry and mitochondrial activity assays indicated that these effects were not due to major shifts in mitotic index or bioenergetic status. Altogether, our results demonstrate that TRIM28, rather than CD133, functions as a central regulator of CSC-associated phenotypes in colorectal cancer. These findings highlight the importance of epigenetic context in CSC biology and may inform the development of more effective therapeutic strategies. Full article
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