Control of AC133/CD133 and impact on human hematopoietic progenitor cells through nucleolin

Bhatia, Sanil; Reister, Sven; Mahotka, Csaba; Meisel, Roland; Grinstein, Edgar

doi:10.1038/leu.2015.146

Cited by 26 publications

(37 citation statements)

References 60 publications

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“…Nucleolin affects mRNA turnover by interacting with the 3′-untranslated region of several target mRNAs. In particular, since Nucleolin has been reported to bind the mRNAs encoding for Bcl2 25 and Akt 26 , its inhibition could result in a destabilization of these two mRNA and, consequently, in a decrement of the amount of the corresponding proteins. Accordingly, by means of qRT-PCR (Real-Time Quantitative Polymerase Chain Reaction) and western blot analysis, we found that Jurkat cells treated with 5 µM oridonin or vehicle for 3 h and 6 h displayed reduced levels of mRNAs of Bcl-2 and Akt (Fig.…”

Section: Resultsmentioning

confidence: 99%

The anti-tumor diterpene oridonin is a direct inhibitor of Nucleolin in cancer cells

Vasaturo

Cotugno

Fiengo

et al. 2018

Sci Rep

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The bioactive plant diterpene oridonin displays important pharmacological activities and is widely used in traditional Chinese medicine; however, its molecular mechanism of action is still incompletely described. In vitro and in vivo data have demonstrated anti-tumor activity of oridonin and its ability to interfere with several cell pathways; however, presently only the molecular chaperone HSP70 has been identified as a direct potential target of this compound. Here, using a combination of different proteomic approaches, innovative Cellular Thermal Shift Assay (CETSA) experiments, and classical biochemical methods, we demonstrate that oridonin interacts with Nucleolin, effectively modulating the activity of this multifunctional protein. The ability of oridonin to target Nucleolin and/or HSP70 could account for the bioactivity profile of this plant diterpene. Recently, Nucleolin has attracted attention as a druggable target, as its diverse functions are implicated in pathological processes such as cancer, inflammation, and viral infection. However, up to now, no small molecule as Nucleolin binders has been reported, thus our finding represents the first evidence of Nucleolin modulation by a small inhibitor.

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Section: Resultsmentioning

confidence: 99%

The anti-tumor diterpene oridonin is a direct inhibitor of Nucleolin in cancer cells

Vasaturo

Cotugno

Fiengo

et al. 2018

Sci Rep

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“…A previous study reported that genetic disruption of PRL-3 reduces clonogenicity and growth of CD133 þ mouse colon cancer cells in an in vitro culture system (34). CD133 is also a specific marker for human hematopoietic stem/progenitor cells (35,36). The observations from these published studies indicate a possibility that aberrant expression of PRL family in hematopoietic cells may promote the transformation of LSC in AML.…”

Section: Discussionmentioning

confidence: 59%

LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell–like Transcriptional Program in AML

Zhou

Chan

et al. 2017

Molecular Cancer Research

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PRL-3 (PTP4A3), a metastasis-associated phosphatase, is also upregulated in patients with acute myeloid leukemia (AML) and is associated with poor prognosis, but the underlying molecular mechanism is unknown. Here, constitutive expression of PRL-3 in human AML cells sustains leukemogenesis in vitro and in vivo. Furthermore, PRL-3 phosphatase activity dependently upregulates LIN28B, a stem cell reprogramming factor, which in turn represses the let-7 mRNA family, inducing a stem cell-like transcriptional program. Notably, elevated levels of LIN28B protein independently associate with worse survival in AML patients. Thus, these results establish a novel signaling axis involving PRL-3/LIN28B/let-7, which confers stem cell-like properties to leukemia cells that is important for leukemogenesis. Implications:The current study offers a rationale for targeting PRL-3 as a therapeutic approach for a subset of AML patients with poor prognosis. Mol Cancer Res; 15(3); 294-303. Ó2016 AACR.

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“…In particular, the bone marrow-derived hematopoietic progenitor cells (HPC) are involved in the initiation of metastases [5]. HPCs are primitive cells predominantly in hematopoietic tissues, such as the bone marrow and umbilical cord blood (UCB) [6][7][8]. HPCs can proliferate and differentiate into various kinds of blood cells.…”

Section: Introductionmentioning

confidence: 99%

Human CD133-positive hematopoietic progenitor cells enhance the malignancy of breast cancer cells

et al. 2020

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Background Human CD133+ hematopoietic progenitor cells (HPCs) are a specific subset of cells that can regulate tumor malignancy. However, the mechanism by which CD133+ HPCs affect the malignancy of human breast cancer has not been reported. Methods CD133+ HPCs were isolated and purified from human umbilical cord blood (UCB). We used in vitro culture of MCF-7 and MDA-MB-231 cell lines, and MCF-7 and MDA-MB-231 cells in nude mice to evaluate whether CD133+ HPCs affected the apoptosis, proliferation, invasion and epithelial mesenchymal transition EMT of breast cancer cells. Results Co-culture with CD133+ HPCs, but not UCB CD133- cells, promoted the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells, accompanied by reducing in vitro spontaneous apoptosis. Co-administration of these two lines with CD133+ HPCs significantly enhanced the growth of implanted breast cancer in vivo. Furthermore, co-culture with CD133+ HPCs, enhanced the invasion of breast cancer cells, N-cadherin and Vimentin expression, but reduced E-cadherin expression in breast cancer cells. Conclusions Our study demonstrated that CD133+ HPCs enhance the malignancy of breast cancer cells by attenuating spontaneous apoptosis and promoting the process of epithelial mesenchymal transition. These findings may provide new insights into the role of human CD133+ HPCs in breast cancer pathogenesis. Therefore, CD133+ HPCs may be a new therapeutic target for inhibiting the progression of breast cancer.

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Control of AC133/CD133 and impact on human hematopoietic progenitor cells through nucleolin

Cited by 26 publications

References 60 publications

The anti-tumor diterpene oridonin is a direct inhibitor of Nucleolin in cancer cells

The anti-tumor diterpene oridonin is a direct inhibitor of Nucleolin in cancer cells

LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell–like Transcriptional Program in AML

Human CD133-positive hematopoietic progenitor cells enhance the malignancy of breast cancer cells

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