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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yu, Y; Tian, L; Feng, X; Cheng, J; Gong, Y; Liu, X; Zhang, Z; Yang, X; He, S; Li, C-Y; Huang, Q

Published Date

  • May 28, 2016

Published In

Volume / Issue

  • 375 / 1

Start / End Page

  • 31 - 38

PubMed ID

  • 26945967

Pubmed Central ID

  • 26945967

Electronic International Standard Serial Number (EISSN)

  • 1872-7980

Digital Object Identifier (DOI)

  • 10.1016/j.canlet.2016.02.052

Language

  • eng

Conference Location

  • Ireland