Skip to main content
Journal cover image

Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.

Publication ,  Journal Article
Wang, Y; Zhao, M; He, S; Luo, Y; Zhao, Y; Cheng, J; Gong, Y; Xie, J; Wang, Y; Hu, B; Tian, L; Liu, X; Li, C; Huang, Q
Published in: J Exp Clin Cancer Res
November 9, 2019

BACKGROUND: Tumor cell repopulation after radiotherapy is a major cause for the tumor radioresistance and recurrence. This study aims to investigate the underlying mechanism of tumor repopulation after radiotherapy, with focus on whether and how necroptosis takes part in this process. METHODS: Necroptosis after irradiation were examined in vitro and in vivo. And the growth-promoting effect of necroptotic cells was investigated by chemical inhibitors or shRNA against necroptosis associated proteins and genes in in vitro and in vivo tumor repopulation models. Downstream relevance factors of necroptosis were identified by western blot and chemiluminescent immunoassays. Finally, the immunohistochemistry staining of identified necroptosis association growth stimulation factor was conducted in human colorectal tumor specimens to verify the relationship with clinical outcome. RESULTS: Radiation-induced necroptosis depended on activation of RIP1/RIP3/MLKL pathway, and the evidence in vitro and in vivo demonstrated that the inhibition of necroptosis attenuated growth-stimulating effects of irradiated tumor cells on living tumor reporter cells. The JNK/IL-8 were identified as downstream molecules of pMLKL during necroptosis, and inhibition of JNK, IL-8 or IL-8 receptor significantly reduced tumor repopulation after radiotherapy. Moreover, the high expression of IL-8 was associated with poor clinical prognosis in colorectal cancer patients. CONCLUSIONS: Necroptosis associated tumor repopulation after radiotherapy depended on activation of RIP1/RIP3/MLKL/JNK/IL-8 pathway. This novel pathway provided new insight into understanding the mechanism of tumor radioresistance and repopulation, and MLKL/JNK/IL-8 could be developed as promising targets for blocking tumor repopulation to enhance the efficacy of colorectal cancer radiotherapy.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Exp Clin Cancer Res

DOI

EISSN

1756-9966

Publication Date

November 9, 2019

Volume

38

Issue

1

Start / End Page

461

Location

England

Related Subject Headings

  • Signal Transduction
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • RNA-Binding Proteins
  • Protein Kinases
  • Oncology & Carcinogenesis
  • Nuclear Pore Complex Proteins
  • Neoplasms
  • Necroptosis
  • Molecular Imaging
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, Y., Zhao, M., He, S., Luo, Y., Zhao, Y., Cheng, J., … Huang, Q. (2019). Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway. J Exp Clin Cancer Res, 38(1), 461. https://doi.org/10.1186/s13046-019-1423-5
Wang, Yiwei, Minghui Zhao, Sijia He, Yuntao Luo, Yucui Zhao, Jin Cheng, Yanping Gong, et al. “Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.J Exp Clin Cancer Res 38, no. 1 (November 9, 2019): 461. https://doi.org/10.1186/s13046-019-1423-5.
Wang Y, Zhao M, He S, Luo Y, Zhao Y, Cheng J, et al. Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway. J Exp Clin Cancer Res. 2019 Nov 9;38(1):461.
Wang, Yiwei, et al. “Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.J Exp Clin Cancer Res, vol. 38, no. 1, Nov. 2019, p. 461. Pubmed, doi:10.1186/s13046-019-1423-5.
Wang Y, Zhao M, He S, Luo Y, Zhao Y, Cheng J, Gong Y, Xie J, Hu B, Tian L, Liu X, Li C, Huang Q. Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway. J Exp Clin Cancer Res. 2019 Nov 9;38(1):461.
Journal cover image

Published In

J Exp Clin Cancer Res

DOI

EISSN

1756-9966

Publication Date

November 9, 2019

Volume

38

Issue

1

Start / End Page

461

Location

England

Related Subject Headings

  • Signal Transduction
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • RNA-Binding Proteins
  • Protein Kinases
  • Oncology & Carcinogenesis
  • Nuclear Pore Complex Proteins
  • Neoplasms
  • Necroptosis
  • Molecular Imaging
  • Mice