Cancer Stem Cells: Acquisition, Characteristics, Therapeutic Implications, Targeting Strategies and Future Prospects

Yadav, Anoop; Desai, Neetin

doi:10.1007/s12015-019-09887-2

Cited by 90 publications

(86 citation statements)

References 233 publications

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“…Numerous environmental conditions and multi-step processes are associated with the initiation and development of tumors. 42,43 Previous research has shown that levels of IL-6 were increased in the serum of patients with osteosarcoma. 44 Qin et al further reported that IL-6 acts as a major upstream molecule that triggers the induction of neoplastic OPN.…”

Section: Discussionmentioning

confidence: 99%

<p>Cinobufagin Suppresses The Characteristics Of Osteosarcoma Cancer Cells By Inhibiting The IL-6-OPN-STAT3 Pathway</p>

Zhang¹,

Ma²,

Li³

2019

DDDT

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Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/a2KF0PMRBDo Background: Current clinical treatments for osteosarcoma are limited by disease recurrence and primary or secondary chemoresistance. Cancer stem-like cells have been proposed to facilitate the initiation, progression, recurrence and chemoresistance of osteosarcoma. Furthermore, previous studies have reported that IL-6-STAT3 pathway is overexpressed in various types of cancer and contributes to cell proliferation, apoptosis, invasion/migration, chemoresistance and modulation of stemness features. Aim: To examined the effect of cinobufagin on cancer progression and modulation of stemness features in osteosarcoma, and investigated the molecular mechanisms underlying such effects. Methods: Human osteosarcoma cell lines U2OS/MG-63 were recruited in this study. Cell proliferation, migration, and invasion were determined by MTT assay, colony formation assay,wound healing assay, and cell invasion assay respectively. Its effect on stemness was assessed by flow cytometry and mammosphere formation. The protein expression levels of related proteins were detected by Western blot. The xenograft model, immunofluorescence staining and immunohistochemistry were used to determine the effect of cinobufagin on tumorigenicity in vivo experiment. Results: We found that cinobufagin suppressed the viability of U2OS/MG-63 spheroids/ parent cells in a time-and dose-dependent manner. Notably, cinobufagin had no effect on the viability of hFOB 1.19 cells. Moreover, cinobufagin induced apoptosis, increased the width of wounds, reduced invasive osteosarcoma spheroids/parent cell numbers and reduced EMT phenotype and OPN levels in U2OS/MG-63 spheroids as well as U2OS/MG-63 parent cells lines. Noticeablely, we found that OPN levels were higher in spheroids group than that in parent cells. In addition, cinobufagin ameliorated the proportion of CD133-positive cells, the size of spheroids and Nanog, Sox-2 and Oct3/4 protein levels. Our in vivo experiments showed that cinobufagin consistently reduced tumor volume,the expressions of OPN, Sox-2, Oct3/4, Nanog and p-STAT3 by the immuno histochemistry staining as well as CD133 expression in tumor tissues by immunofluorescence analysis. From a mechanistic point of view, cinobufagin was shown to inhibit IL-6-OPN-STAT3 signaling pathway. Exogenous IL-6/OE-OPN/overexpression STAT3 attenuated the induction of cinobufagin-mediated apoptosis and the suppression of stemness properties respectively. Conclusion: Collectively, our data demonstrated that cinobufagin inhibited the viability and tumorigenesis capability of osteosarcoma cells by blocking IL-6-OPN-STAT3 signaling pathway. Cinobufagin may therefore represent a promising therapeutic agent for osteosarcoma management.

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Section: Discussionmentioning

confidence: 99%

<p>Cinobufagin Suppresses The Characteristics Of Osteosarcoma Cancer Cells By Inhibiting The IL-6-OPN-STAT3 Pathway</p>

Zhang¹,

Ma²,

Li³

2019

DDDT

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“…Among them, the WNT pathway is deregulated in epithelial-mesenchymal transition (EMT) and CSCs (13). Mutations in WNT signaling components, such as APC, AXIN, β-catenin, and WNT ligands were first observed in colorectal cancers, but have also been reported in other solid tumors (14)(15)(16)(17)(18)(19)(20)(21) and hematological malignancies, including leukemia and Multiple Myeloma (MM) (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

et al. 2019

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WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies.

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“…Therefore, a better understanding of the underlying mechanism of NPC metastasis is the key to explore novel treatment strategies for patients with this disease. CSCs, a group of "tumor-initiating cells" possessing the capacity to initiate tumor growth, self-renewal properties, and multi-drug resistance, have been found to be highly related to tumor occurrence, development, and metastasis [21]. Over the years, increasing studies have focused on understanding the biological properties and mechanisms of CSC formation to develop novel strategies to identify these stem-like cancer cells and to target them specifically [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting

Chen

Wang

et al. 2020

J Exp Clin Cancer Res

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Background: Recurrence and distant metastasis are still the main factors leading to treatment failure for malignant tumors including nasopharyngeal carcinoma (NPC). Therefore, elucidating the molecular mechanisms underlying nasopharyngeal carcinoma metastasis is of great clinical significance for targeted gene therapy and prognostic evaluation. PinX1, a tumor suppressor gene, was previously demonstrated to be a powerful tool for targeting telomerase in order to resist malignant tumor proliferation and migration. The aim of this study was to explore the mechanism through which PinX1 regulates epithelial-mesenchymal transition (EMT) and tumor metastasis in NPC and investigate its clinical significance and biological role with respect to disease progression.Methods: Cell Counting Kit-8 (CCK8), Transwell assays, Colony formation analysis and Xenograft tumorigenicity assay were used to measure the nasopharyngeal CD133 + cancer stem cell proliferation, migration, and invasion abilities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were conducted to investigate the underlying mechanism that PinX1 inhibits cell proliferation, migration, and invasion via regulating EMT in nasopharyngeal CD133 + CSCs. Results: We found that the overexpression of PinX1 and P53 inhibited cell proliferation, migration, and invasion, but that the inhibition of miR-200b blocked these effects, in nasopharyngeal CD133 + cancer stem cells (CSCs). Mechanistic investigations elucidated that PinX1 inhibits cell proliferation, migration, and invasion by regulating the P53/miR-200b-mediated transcriptional suppression of Snail1, Twist1, and Zeb1, consequently inhibiting EMT in nasopharyngeal CD133 + CSCs. Conclusions: Our findings indicate that PinX1 inhibits cell proliferation, migration, and invasion via P53/miR-200bregulated EMT in the malignant progression of human NPC, which might suggest novel clinical implications for disease treatment.

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Cancer Stem Cells: Acquisition, Characteristics, Therapeutic Implications, Targeting Strategies and Future Prospects

Cited by 90 publications

References 233 publications

<p>Cinobufagin Suppresses The Characteristics Of Osteosarcoma Cancer Cells By Inhibiting The IL-6-OPN-STAT3 Pathway</p>

<p>Cinobufagin Suppresses The Characteristics Of Osteosarcoma Cancer Cells By Inhibiting The IL-6-OPN-STAT3 Pathway</p>

WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

Pin2 telomeric repeat factor 1-interacting telomerase inhibitor 1 (PinX1) inhibits nasopharyngeal cancer cell stemness: implication for cancer progression and therapeutic targeting

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