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Cross-talk between ribosome biogenesis, translation, and mTOR in CD133+ 4/CD44+ prostate cancer stem cells

Clinical and Translational Oncology volume 22, pages 1040–1048 (2020)Cite this article

Abstract

Objective

To investigate the gene expression profile of CSCs and to explore the key pathways and specific molecular signatures involved in the characteristic of CSCs.

Materials and methods

CD133+ /CD44+ CSCs and bulk population (non-CSCs) were isolated from DU-145 cells using fluorescence-activated cell sorting (FACS). We used Illumina HumanHT-12 v4 Expression to investigate gene expression profiling of CSCs and non-CSCs. Protein–protein interaction (PPI) network analysis was performed using the STRING database. Biomarkers selected based on gene expression profiling were visually analyzed using immunofluorescence staining method. An image analysis program, ImageJ®, was used for the analysis of fluorescence intensity.

Results

In microarray analysis, we found that many ribosomal proteins and translation initiation factors that constitute the mTOR complex were highly expressed. PPI analysis using the 33 genes demonstrated that there was a close interaction between ribosome biogenesis, translation, and mTOR signaling. The fluorescence amount of mTOR and MLST8 were higher in CSCs compared to non-CSCs.

Conclusions

The increase in a number of genes associated with ribosome biogenesis, translation, and mTOR signaling may be important to evaluate prognosis and determine treatment approach for prostate cancer (PCa). A better understanding of the molecular pathways associated with CSCs may be promising to develop targeted therapies to prolong survival in PCa.

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Abbreviations

ATCC:

American Type Culture Collection

CSC:

Cancer stem cell

DAPI:

4′,6-Diamidino-2-phenylindole

DEGs:

Differentially expressed genes

DU-145:

Prostate cancer cell lines

DU-145 CSC:

DU-145 cancer stem cell

DU-145 non-CSC:

DU-145 non-cancer stem cell (bulk population)

ERG:

Erythroblastosis virus oncogene

FACS:

Fluorescence-activated cell separation

mTOR:

Mammalian target of rapamycin

PBS:

Phosphate-buffered saline

PCa:

Prostate cancer

PI3K:

Phosphatidylinositol 3-kinase

PPI:

Protein–protein interaction

SC:

Stem cell

TMPRSS2:

Androgen-regulated transmembrane serine protease gene

ULK1:

Homo sapiens unc-51-like kinase 1

ULK2:

Homo sapiens unc-51-like kinase 2

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Authors and Affiliations

  1. Department of Urology, Faculty of Medicine, Ege University School of Medicine, Ege University, Bornova, PO Box: 35100, 35100, İzmir, Turkey

    Z. Binal, F. Kızılay & B. Altay

  2. Department of Histology and Embryology, Faculty of Medicine, Yuzuncu Yıl University, 65080, Van, Turkey

    E. Açıkgöz

  3. Department of Histology and Embryology, Faculty of Medicine, Ege University, 35100, Izmir, Turkey

    G. Öktem

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  1. Z. Binal
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  2. E. Açıkgöz
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  3. F. Kızılay
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  4. G. Öktem
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Contributions

Z Binal, E Acikgoz, G Oktem: Protocol/project development; Z Binal, E Acikgoz, F Kızılay, G Oktem, B Altay: Data collection or management; E Acikgoz, F Kızılay: Data analysis; Z Binal, E Acikgoz, F Kızılay, B Altay: Manuscript writing/editing.

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Correspondence to F. Kızılay.

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The authors declared that the research was conducted according to the principles of the World Medical Association Declaration of Helsinki “Ethical Principles for Medical Research Involving Human Subjects” (amended in October 2013).

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Cite this article

Binal, Z., Açıkgöz, E., Kızılay, F. et al. Cross-talk between ribosome biogenesis, translation, and mTOR in CD133+ 4/CD44+ prostate cancer stem cells. Clin Transl Oncol 22, 1040–1048 (2020). https://doi.org/10.1007/s12094-019-02229-1

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  • DOI: https://doi.org/10.1007/s12094-019-02229-1

Keywords

  • Prostate cancer
  • Cancer stem cell
  • Ribosomal proteins
  • Translation
  • mTOR