Open Access

STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells

  • Authors:
    • Li Lin
    • David Jou
    • Yina Wang
    • Haiyan Ma
    • Tianshu Liu
    • James Fuchs
    • Pui-Kai Li
    • Jiagao Lü
    • Chenglong Li
    • Jiayuh Lin
  • View Affiliations

  • Published online on: October 12, 2016     https://doi.org/10.3892/ijo.2016.3728
  • Pages: 2265-2274
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer including pancreatic cancer. Whether STAT3 is activated in stem cell-like pancreatic cancer cells and the effect of STAT3 inhibition, is still unknown. Flow cytometry was used to isolate pancreatic cancer stem-like cells which are identified by both aldehyde dehydrogenase (ALDH)-positive (ALDH+) as well as cluster of differentiation (CD) 44-positive/CD24-positive subpopulations (CD44+/CD24+). STAT3 activation and the effects of STAT3 inhibition by STAT3 inhibitors, LLL12, FLLL32, and Stattic in ALDH+ and CD44+/CD24+ cells were examined. Our results showed that ALDH+ and CD44+/CD24+ pancreatic cancer stem-like cells expressed higher levels of phosphorylated STAT3, an active form of STAT3, compared to ALDH-negative (ALDH-) and CD44-negative/CD24-negative (CD44-/CD24-) pancreatic cancer cells, suggesting that STAT3 is activated in pancreatic cancer stem-like cells. Small molecular STAT3 inhibitors inhibited STAT3 phosphorylation, STAT3 downstream target gene expression, cell viability, and tumorsphere formation in ALDH+ and CD44+/CD24+ cells. Our results indicate that STAT3 is a novel therapeutic target in pancreatic cancer stem-like cells and inhibition of activated STAT3 in these cells by STAT3 inhibitors may offer an effective treatment for pancreatic cancer.

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December 2016
Volume 49 Issue 6

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Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J. ... Lin, J. (2016). STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells. International Journal of Oncology, 49, 2265-2274. https://doi.org/10.3892/ijo.2016.3728
MLA
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J., Li, P., Lü, J., Li, C., Lin, J."STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells". International Journal of Oncology 49.6 (2016): 2265-2274.
Chicago
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J., Li, P., Lü, J., Li, C., Lin, J."STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells". International Journal of Oncology 49, no. 6 (2016): 2265-2274. https://doi.org/10.3892/ijo.2016.3728