Resetting cancer stem cell regulatory nodes upon
            <scp>MYC</scp>
            inhibition

Galardi, Silvia; Savino, Mauro; Scagnoli, Fiorella; Pellegatta, Serena; Pisati, Federica; Zambelli, Federico; Illi, Barbara; Annibali, Daniela; Beji, Sara; Orecchini, Elisa; Alberelli, Maria Adele; Apicella, Clara; Fontanella, Rosaria Anna; Michienzi, Alessandro; Finocchiaro, Gaetano; Farace, Maria Giulia; Pavesi, Giulio; Ciafrè, Silvia Anna; Nasi, Sergio

doi:10.15252/embr.201541489

Cited by 52 publications

(59 citation statements)

References 72 publications

(167 reference statements)

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“…This result was consistent with a previous study which suggested that MYC correlated with cancer stem cell properties [56, 57]. Transcripts of MYC could not be exclusively attributed to Notch activation due to the dim expression of Notch3 in the suspended lymphoma cells.…”

Section: Discussionsupporting

confidence: 93%

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Lin¹,

Chen²,

Wu³

et al. 2018

Acta Haematol

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Background/Aims: Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. Methods: We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. Results: Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. Conclusion: Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells.

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Section: Discussionsupporting

confidence: 93%

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Lin¹,

Chen²,

Wu³

et al. 2018

Acta Haematol

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“…It has been reported that MIAT is selectively upregulated in neuroendocrine prostate cancer and may interact with polycomb genes [16]. Myc inhibition could increase the expression of MIAT in glioblastoma cells [31]. Luan et al have found that MIAT promotes breast cancer progression and functions as a ceRNA to regulate DUSP7 expression by sponging miR-155-5p [24].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

Qü¹,

Xiao²,

Xiao³

et al. 2018

Cell Physiol Biochem

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Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC.

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“…The overexpression of MYC in normal human cells may be ineffective or highly destructive, resulting in stagnation of proliferation, aging, or apoptosis. 110 MYC is usually deregulated in human cancers, plays an important role in maintaining the number of invasive CSCs, 111 and is also one of the most effective oncogenes for detecting the cell transformation phenotype in vitro and in vivo. Previous studies have shown that deletion of the tumor suppressor gene p53 and MYC synergizes to induce hepatocyte proliferation and tumorigenesis.…”

Section: Major Transcription Factors In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,246

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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Resetting cancer stem cell regulatory nodes upon MYC inhibition

Cited by 52 publications

References 72 publications

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

Targeting cancer stem cell pathways for cancer therapy

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