Thymosin β4 targeting impairs tumorigenic activity of colon cancer stem cells

Ruggero De Maria Marchiano, Alfredo Pagliuca, Lucia Ricci-Vitiani, Cristiana Mollinari, Simona Di Martino, Mauro Biffoni, Emanuela Pilozzi, Maria Chiara De Stefano, Rita Circo, Daniela Merlo, Enrico Garaci

Risultato della ricerca: Contributo in rivistaArticolo in rivista

28 Citazioni (Scopus)

Abstract

Thymosin β4 (Tβ4) is an actin-binding peptide overexpressed in several tumors, including colon carcinomas. The aim of this study was to investigate the role of Tβ4 in promoting the tumorigenic properties of colorectal cancer stem cells (CR-CSCs), which are responsible for tumor initiation and growth. We first found that CR-CSCs from different patients have higher Tβ4 levels than normal epithelial cells. Then, we used a lentiviral strategy to down-regulate Tβ4 expression in CR-CSCs and analyzed the effects of such modulation on proliferation, survival, and tumorigenic activity of CR-CSCs. Empty vector-transduced CR-CSCs were used as a control. Targeting of the Tβ4 produced CR-CSCs with a lower capacity to grow and migrate in culture and, interestingly, reduced tumor size and aggressiveness of CR-CSC-based xenografts in mice. Moreover, such loss in tumorigenic activity was accompanied by a significant increase of phosphatase and tensin homologue (PTEN) and a concomitant reduction of the integrin-linked kinase (ILK) expression, which resulted in a decreased activation of protein kinase B (Akt). Accordingly, exogenous expression of an active form of Akt rescued all the protumoral features lost after Tβ4 targeting in CR-CSCs. In conclusion, Tβ4 may have important implications for therapeutic intervention for treatment of human colon carcinoma. © FASEB.
Lingua originaleEnglish
pagine (da-a)4291-4301
Numero di pagine11
RivistaTHE FASEB JOURNAL
Volume24
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Actin cytoskeleton
  • Animals
  • Biochemistry
  • Biotechnology
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell cycle
  • Cells, Cultured
  • Colonic Neoplasms
  • Down-Regulation
  • Epithelial Cells
  • Gene Expression Regulation, Neoplastic
  • Genetics
  • Humans
  • Lentivirus
  • Medicine (all)
  • Mice
  • Mice, SCID
  • Molecular Biology
  • Neoplastic Stem Cells
  • Oncogene Protein v-akt
  • PTEN Phosphohydrolase
  • Protein-Serine-Threonine Kinases
  • Target therapy
  • Thymosin
  • Tumor growth

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