STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH +/CD133 + stem cell-like human colon cancer cells

Li Lin, James Fuchs, Chenglong Li, Veronica Olson, Tanios Bekaii-Saab, Jiayuh Lin

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH +/CD133 +). The effects of STAT3 inhibition in colon cancer stem-like cells were examined.The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and -4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem-like cells and inhibition of STAT3 in cancer stem-like cells may offer a potential treatment for colorectal cancer.

Original languageEnglish (US)
Pages (from-to)246-251
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume416
Issue number3-4
DOIs
StatePublished - Dec 16 2011

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Keywords

  • ALDH
  • CD133
  • Cancer stem-like cells
  • Colon cancer
  • Curcumin analog
  • FLLL32
  • STAT3

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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