Cancer stem cells in progression of colorectal cancer

Zhou, Yujuan; Xia, Longzheng; Wang, Heran; Oyang, Linda; Su, Min; Liu, Qiang; Lin, Jingguan; Tan, Shiming; Tian, Yutong; Liao, Qianjin; Cao, Deliang

doi:10.18632/oncotarget.23607

Cited by 189 publications

(140 citation statements)

References 120 publications

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“…CSCs may, in part, also contribute to therapeutic resistance leading to tumor recurrence and tumor progression. Multiple surface markers have been identified for colorectal CSCs, although almost every one of them appears to be enriching for a population of cells with stem cell-related properties 39 . CD44 is involved in malignant progression, making cells less sensitive to apoptotic signals and chemoresistance in cancer 39,40 .…”

Section: Discussionmentioning

confidence: 99%

“…Multiple surface markers have been identified for colorectal CSCs, although almost every one of them appears to be enriching for a population of cells with stem cell-related properties 39 . CD44 is involved in malignant progression, making cells less sensitive to apoptotic signals and chemoresistance in cancer 39,40 . The standard CD44s isoform has a molecular weight of 85 kDa, while several CD44 variant isoforms (CD44v) have been reported from 85-200 kDa in cancer 41 .…”

Section: Discussionmentioning

confidence: 99%

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Cucurbitacin B and I inhibits colon cancer growth by targeting the Notch signaling pathway

Dandawate

Subramaniam

Panovich

et al. 2020

Sci Rep

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cancer stem cells (cScs) have the ability to self-renew and induce drug resistance and recurrence in colorectal cancer (cRc). As current chemotherapy doesn't eliminate cScs completely, there is a need to identify novel agents to target them. We investigated the effects of cucurbitacin B (C-B) or I (C-I), a natural compound that exists in edible plants (bitter melons, cucumbers, pumpkins and zucchini), against cRc. c-B or c-i inhibited proliferation, clonogenicity, induced G 2 /M cell-cycle arrest and caspase-mediated-apoptosis of cRc cells. c-B or c-i suppressed colonosphere formation and inhibited expression of CD44, DCLK1 and LGR5. These compounds inhibited notch signaling by reducing the expression of Notch 1-4 receptors, their ligands (Jagged 1-2, DLL1,3,4), γ-secretase complex proteins (Presenilin 1, Nicastrin), and downstream target Hes-1. Molecular docking showed that C-B or C-I binds to the ankyrin domain of Notch receptor, which was confirmed using the cellular thermal shift assay. finally, c-B or c-i inhibited tumor xenograft growth in nude mice and decreased the expression of cScmarkers and notch signaling proteins in tumor tissues. together, our study suggests that c-B and c-i inhibit colon cancer growth by inhibiting notch signaling pathway. Colorectal cancer (CRC) is the third most commonly diagnosed cancer with an estimated 145600 new cases and 51020 deaths estimated to occur in the United States in 2019 1. A significant concern is that the frequency of individuals diagnosed with colon cancer below 50 years of age is steadily rising every year 2. Adjuvant chemotherapy and radiotherapy post-surgery is the primary choice of treatment for advanced CRC 3. Cancer stem cells (CSCs) are rare in number and possess the ability to self-renew with the capacity to generate a tumor 4,5. They also develop chemo-and radio-resistance, contributing to tumor progression and recurrence. As current chemotherapy is not able to achieve complete eradication of CSCs 6 , it is crucial to develop novel non-toxic drug therapies that effectively target both CSCs and proliferating cancer cells. CSC markers identified in CRC, include CD44, leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), c-Myc, ABCG2, CD133, ALDH1A1, epithelial cell adhesion molecule (EpCAM) and doublecortin-like kinase-1 (DCLK1) 7. CSCs rely on classic signaling pathways for growth such as the Notch signaling that plays an important role in transformation and CSC self-renewal 8. The Notch pathway consists of five ligands (Jagged-1, Jagged-2 and Delta-like ligands −1, −3 and −4 (Dll-1, −3 and −4) and four receptors (Notch 1-4) 9. Upon ligand binding, Notch receptors are cleaved twice. The first cleavage by ADAM/TACE is followed by a second cleavage by the γ-secretase enzyme complex releasing Notch intracellular domain (NICD). The NICD binds to MAML1-CSL-HAT-P300 complex to induce the target gene expression including but not limited to HES1, HEY1, Cyclin D1 and c-Myc 9. Hence, targeting the Notch signaling pathway may be an effective mechanism...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cucurbitacin B and I inhibits colon cancer growth by targeting the Notch signaling pathway

Dandawate

Subramaniam

Panovich

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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Section: Colon Cancer Stem Cellsmentioning

confidence: 99%

“…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. CCSCs acquire accumulated mutations in specific oncogenes and tumor suppressor genes that confer them different erratic abilities such as stemness, producing actively proliferating cancer progenitor cells, multidrug resistance, radioresistance, apoptosis resistance, enhanced DNA repair capacity, and some phenotypic characteristics, such as expression of special cell surface markers, which are used for their isolation (Zhou et al, ). Identifying the origin of CCSCs might be useful for designing an effective therapy; however, there are many contradictions about the source of tumor‐initiating cells/CSCs and they may arise from the colon stem cells, colon progenitor cells, normal tumor cells, or other dedifferentiated somatic cells inside the intestine that acquire malignant molecular and cellular changes because of various carcinogenic genetic (internal or external) and environmental factors by the time and their diversity and evolution result from clonal evolution model (sequential cycles of genetic/epigenetic changes) (Nguyen, Vanner, Dirks, & Eaves, ).…”

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

102

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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

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“…The centrality and essentiality of the cancer cell of origin and the impact of the cancer microenvironment on cell fate decisions, including the metastasis-promoting bidirectional epithelial-to-mesenchymal transition (EMT), have also been investigated and should be key considerations in new targeted therapies [7]. Within this milieu, cancer stem cells (CSC) could not only directly involved as cancer cells of origin, but also in cancer progression and recurrence, cell heterogeneity and resistance to chemotherapy, invasion and metastasis [7][8][9][10]. Recent studies of the roles of CRC cell of origin in mouse models have shown that colorectal adenomas can arise from both undifferentiated stem cells at the bottoms of intestinal crypts and from transit-amplifying differentiated cells, although with different disease courses, implying that the CRC phenotype and related therapeutic strategies are dependent on the cellular and molecular backgrounds of the cell of origin, as well as on cellular microenvironment [11,12].…”

Section: Introductionmentioning

confidence: 99%

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

et al. 2020

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Copyright: Farace et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACTColorectal cancer (CRC) is a deadly tumour in Western countries characterized by high cellular/molecular heterogeneity. Cancer stem cells (CSC) act in cancer recurrence, drug-resistance and in metastatic epithelial-to-mesenchymal transition. microRNAs (miRNAs) contribute to cancer is increasing, and miRNA roles in CSC phenotype and fate and their utility as CRC biomarkers have also been reported. Here, we investigated miR-21, miR-221, miR-18a, miR-210, miR-31, miR-34a, miR-10b and miR-16 expression in experimental ALDH + and CD44 + /CD326 + colorectal CSCs obtained from the human CRC cell lines HCT-116, HT-29 and T-84. Then, we moved our analysis in cancer tissue (CT), healthy tissue (HT) and serum (S) of adult CRC patients (n=12), determining relationships with clinical parameters (age, sex, metastasis, biochemical serum markers). Specific miRNA patterns were evident in vitro (normal, monolayers and CSCs) and in patients' samples stratified by TNM stage (LOW vs HIGH) or metastasis (Met vs no-Met). miR-21, miR-210, miR-34a upregulation ad miR-16 dowregulation associated with the CSCs phenotype. miR-31b robustly overexpressed in monolayers and CSCs, and in CT ad S of HIGH grade and Met patients, suggesting a role as marker of CRC progression and metastasis. miR-18a upregulated in all cancer models and associated to CSC phenotype, and to metastasis and age in patients. miR-10b downregulated in CT and S of LOW/HIGH grade and no-Met patients. Our results identify miRNAs useful as colorectal CSC biomarker and that miR-21, miR-210, miR-10b and miR-31b are promising markers of CRC. A specific role of miR-18a as metastatic CRC serum biomarker in adult patients was also highlighted. www.oncotarget.com

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Cancer stem cells in progression of colorectal cancer

Cited by 189 publications

References 120 publications

Cucurbitacin B and I inhibits colon cancer growth by targeting the Notch signaling pathway

Cucurbitacin B and I inhibits colon cancer growth by targeting the Notch signaling pathway

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

Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients

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