Mesencephalic astrocyte-derived neurotrophic factor is a novel radioresistance factor in mouse B16 melanoma

Yuta Tanaka, Takato Takenouchi, Mitsutoshi Tsukimoto

Research output: Contribution to journalArticlepeer-review

Abstract

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neuroprotective factor produced in response to endoplasmic reticulum (ER) stress induced by various stressors, but its involvement in the radioresistance of tumor cells is unknown. Here, we found that MANF is released after γ-irradiation (2 Gy and 4 Gy) of B16 melanoma cells, and its release was suppressed by 4-phenylbutyric acid, an ER stress inhibitor. MANF was not released after low-dose (1 Gy) γ-irradiation, but pretreatment of 1 Gy-irradiated cells with recombinant MANF enhanced the cellular DNA damage response and attenuated reproductive cell death. In MANF-knockdown cells, the DNA damage response and p53 activation by γ-irradiation (2 Gy) were suppressed, and reproductive cell death was increased. MANF also activated the ERK signaling pathway. Our findings raise the possibility that MANF could be a new target for overcoming radioresistance.

Original languageEnglish
Pages (from-to)869-875
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume524
Issue number4
DOIs
Publication statusPublished - 16 Apr 2020

Keywords

  • DNA repair
  • MANF
  • Melanoma
  • Radiation therapy
  • Radioresistance

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