Cancer stem cells (CSCs) in cancer progression and therapy

Najafi, Masoud; Farhood, Bagher; Mortezaee, Keywan

doi:10.1002/jcp.27740

Cited by 446 publications

(304 citation statements)

References 112 publications

(307 reference statements)

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…Therefore, Lgr5 + CD44 + EpCAM + cells from DLD-1, and seven tissue samples (patient #1, 3,4,6,8,11,12) sorted by flow cytometry were used for further study. Our data showed that the level of KLF4 expression was significantly higher in Lgr5 + CD44 + EpCAM + cells than those of Lgr5 − CD44 − EpCAM − cells ( Figure S1A).…”

Section: Expression Of Klf4 In Lgr5 + Cd44 + Epcam + Colorectal Cscsmentioning

confidence: 99%

See 1 more Smart Citation

Krüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway

Leng

Zhou

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

| INTRODUC TI ONCancer metastasis contributes to approximately 90% of cancer-related deaths. 1 Accumulating evidence indicates that cancer stem cells (CSCs) are responsible for the seeding and colonization of cancer metastasis. 2-4 For the past decades, studies have explored and investigated the mechanisms of human carcinogenesis to help develop novel therapeutic strategies. To date, cancer treatment has not been much improved in advanced and chemo-resistant human cancers. Thus, a better understanding of CSCs behaviour in human cancers, including colorectal cancers (CRC), could provide insight into defining the molecular mechanisms of tumorigenesis and cancer progression. Indeed, identification of CSC markers is a very hot topic and interesting data have been generated. 5 For example, CSC markers for breast, prostate, AbstractKrüppel-like factor 4 (KLF4) was closely associated with epithelial-mesenchymal transition and stemness in colorectal cancer stem cells (CSCs)-enriched spheroid cells.Nonetheless, the underlying molecular mechanism is unclear. This study showed that KLF4 overexpression was accompanied with stemness and mesenchymal features in Lgr5 + CD44 + EpCAM + colorectal CSCs. KLF4 knockdown suppressed stemness, mesenchymal features and activation of the TGF-β1 pathway, whereas enforced KLF4 overexpression activated TGF-β1, phosphorylation of Smad 2/3 and Snail expression, and restored stemness and mesenchymal phenotypes. Furthermore, TGF-β1 pathway inhibition invalidated KLF4-facilitated stemness and mesenchymal features without affecting KLF4 expression. The data from the current study are the first to demonstrate that KLF4 maintains stemness and mesenchymal properties through the TGF-β1/Smad/Snail pathway in Lgr5 + CD44 + EpCAM + colorectal CSCs. K E Y W O R D Scancer stem cell, colorectal cancer, Krüppel-like factor 4, snail, TGF-β1

show abstract

Section: Expression Of Klf4 In Lgr5 + Cd44 + Epcam + Colorectal Cscsmentioning

confidence: 99%

“…8,9 For example, in CRC, TGF-β1 highly expression promoted cancer progression by Smad signalling. 8,9 For example, in CRC, TGF-β1 highly expression promoted cancer progression by Smad signalling.…”

mentioning

confidence: 99%

Krüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway

Leng

Zhou

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Also, cancer-associated fibroblasts, one of the most influential cell types in the tumor stroma, can promote a CSC-like phenotype [8]. Furthermore, the special configuration of the SC niche contributes to the resistance of CSCs to standard chemotherapy and radiotherapy and thus to relapse after treatment [1,2,8]. As will be demonstrated in the following sections, PGs and glycosaminoglycans (GAGs) have emerged as important modulators of the cancer SC phenotype, and as novel therapeutic targets in malignant disease.…”

Section: Introductionmentioning

confidence: 99%

Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance

et al. 2019

View full text Add to dashboard Cite

In contrast to the bulk of the tumor, a subset of cancer cells called cancer stem cells (CSC; or tumor‐initiating cells) is characterized by self‐renewal, unlimited proliferative potential, expression of multidrug resistance proteins, active DNA repair capacity, apoptosis resistance, and a considerable developmental plasticity. Due to these properties, CSCs display increased resistance to chemo‐ and radiotherapy. Recent findings indicate that aberrant functions of proteoglycans (PGs) and glycosaminoglycans (GAGs) contribute substantially to the CSC phenotype and therapeutic resistance. In this review, we summarize how the diverse functions of the glycoproteins and carbohydrates facilitate acquisition and maintenance of the CSC phenotype, and how this knowledge can be exploited to develop novel anticancer therapies. For example, the large transmembrane chondroitin sulfate PG NG2/CSPG4 marks stem cell (SC) populations in brain tumors. Cell surface heparan sulfate PGs of the syndecan and glypican families modulate the stemness‐associated Wnt, hedgehog, and notch signaling pathways, whereas the interplay of hyaluronan in the SC niche with CSC CD44 determines the maintenance of stemness and promotes therapeutic resistance. A better understanding of the molecular mechanisms by which PGs and GAGs regulate CSC function will aid the development of targeted therapeutic approaches which could avoid relapse after an otherwise successful conventional therapy. Chimeric antigen receptor T cells, PG‐primed dendritic cells, PG‐targeted antibody–drug conjugates, and inhibitory peptides and glycans have already shown highly promising results in preclinical models.

show abstract

“…Cancer stem cells (CSCs) are a small number of undifferentiated tumorigenic cells inside the tumors with malignant phenotypic characteristics and their existence was empirically proved in the 1990s (Najafi, Farhood, & Mortezaee, ). CCSCs in accordance with other types of CSCs are resistance to therapies and have a higher capacity to form clones in vitro and to generate xenograft tumors in immunodeficient mice.…”

Section: Introductionmentioning

confidence: 99%

Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment

Jahanafrooz

Mosafer

Akbari

et al. 2019

Journal Cellular Physiology

115

View full text Add to dashboard Cite

Despite many advances and optimization in colon cancer treatment, tumor recurrence and metastases make the development of new therapies necessary.Colon cancer stem cells (CCSCs) are considered as the main triggering factor of cancer progression, recurrence, and metastasis. CCSCs as a result of accumulated genetic and epigenetic alterations and also complex interconnection with the tumor microenvironment (TME) can evolve and convert to full malignant cells. Mounting evidence suggests that in cancer therapy both CCSCs and non-CCSCs in TME have to be regarded to break through the limitation of current therapies. In this regard, stem cell capabilities of some non-CCSCs may arise inside the TME condition. Therefore, a deep knowledge of regulatory mechanisms, heterogeneity, specific markers, and signaling pathways of CCSCs and their interconnection with TME components is needed to improve the treatment of colorectal cancer and the patient's life quality. In this review, we address current different targeted therapeutic options that target cell surface markers and signaling pathways of CCSCs and other components of TME.Current challenges and future perspectives of colon cancer personalized therapy are also provided here. Taken together, based on the deep understanding of biology of CCSCs and using three-dimensional culture technologies, it can be possible to reach successful colon cancer eradication and improvise combination targeted therapies against CCSCs and TME. K E Y W O R D Scolon cancer stem cells, colorectal cancer, combination therapy, complex interaction, signaling pathways, tumor microenvironment

show abstract

Cancer stem cells (CSCs) in cancer progression and therapy

Cited by 446 publications

References 112 publications

Krüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway

Krüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway

Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance

Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment

Contact Info

Product

Resources

About