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eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation.

Publication ,  Journal Article
Yu, Y; Tian, L; Feng, X; Cheng, J; Gong, Y; Liu, X; Zhang, Z; Yang, X; He, S; Li, C-Y; Huang, Q
Published in: Cancer Lett
May 28, 2016

Pancreatic cancer is a devastating disease characterized by treatment resistance and high recurrence rate. Repopulation of surviving tumor cells undergoing radiotherapy is one of the most common reasons for recurrence. Our previous studies have discovered a novel mechanism for repopulation after irradiation that activation of caspase-3 in irradiated tumor cells activates PKCδ/p38 axis to transmit proliferation signals promoting repopulation of surviving tumor cells. Here we found Sox2 expression is up-regulated in irradiated pancreatic cancer cells, which played a major role in tumor cell repopulation after irradiation. Over-expression of Sox2 strongly enhanced the growth-stimulating effect of irradiated dying tumor cells on living tumor cells through a paracrine modality. Furthermore, we identified activated eIF4E, which is phosphorylated by MNK1, as a regulator of Sox2 expression after irradiation, and pharmacologic inhibition of eIF4E with CGP57380 and Ribavirin significantly weakened Sox2-mediated tumor cell repopulation. Finally, we showed the activation of caspase 3/PKCδ/p38/MNK1 signal pathway in irradiated pancreatic tumor cells. Together, we showed a novel pathway regulating Sox2 expression and Sox2 may be a promising target to reduce recurrence due to repopulation of surviving tumor cells after radiotherapy.

Duke Scholars

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

May 28, 2016

Volume

375

Issue

1

Start / End Page

31 / 38

Location

Ireland

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • SOXB1 Transcription Factors
  • Radiation Tolerance
  • Protein Processing, Post-Translational
  • Phosphorylation
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
Chicago
ICMJE
MLA
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Yu, Y., Tian, L., Feng, X., Cheng, J., Gong, Y., Liu, X., … Huang, Q. (2016). eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation. Cancer Lett, 375(1), 31–38. https://doi.org/10.1016/j.canlet.2016.02.052
Yu, Yang, Ling Tian, Xiao Feng, Jin Cheng, Yanping Gong, Xinjian Liu, Zhengxiang Zhang, et al. “eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation.Cancer Lett 375, no. 1 (May 28, 2016): 31–38. https://doi.org/10.1016/j.canlet.2016.02.052.
Yu Y, Tian L, Feng X, Cheng J, Gong Y, Liu X, et al. eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation. Cancer Lett. 2016 May 28;375(1):31–8.
Yu, Yang, et al. “eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation.Cancer Lett, vol. 375, no. 1, May 2016, pp. 31–38. Pubmed, doi:10.1016/j.canlet.2016.02.052.
Yu Y, Tian L, Feng X, Cheng J, Gong Y, Liu X, Zhang Z, Yang X, He S, Li C-Y, Huang Q. eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation. Cancer Lett. 2016 May 28;375(1):31–38.
Journal cover image

Published In

Cancer Lett

DOI

EISSN

1872-7980

Publication Date

May 28, 2016

Volume

375

Issue

1

Start / End Page

31 / 38

Location

Ireland

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • SOXB1 Transcription Factors
  • Radiation Tolerance
  • Protein Processing, Post-Translational
  • Phosphorylation
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Humans
  • Gene Expression Regulation, Neoplastic