Methionine restriction breaks obligatory coupling of cell proliferation and death by an oncogene Src in Drosophila

eLife

Yasuhiro Minami¹  Hiroshi Nishida²  Diana M Ho³  Tomoyoshi Soga⁴  Sho Tabata⁴  Lynna Yang⁵  Tomomi Takano⁶  Morihiro Okada⁶  Sa Kan Yoo⁷  Jongkyeong Chung⁸ 

[1] Division of Cell Physiology, Kobe University, Kobe, Japan;Division of Cell Physiology, Kobe University, Kobe, Japan;RIKEN CPR, Kobe, Japan;Harvard Medical School, Boston, United States;Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan;RIKEN CPR, Kobe, Japan;RIKEN CPR, Kobe, Japan;RIKEN BDR, Kobe, Japan;RIKEN CPR, Kobe, Japan;RIKEN BDR, Kobe, Japan;Division of Developmental Biology and Regenerative Medicine, Kobe University, Kobe, Japan;Seoul National University, Seoul, Republic of Korea;

关键词: oncogene;    nutrition;    cell death;    proliferation;    methionine;    D. melanogaster;   

DOI  :  10.7554/eLife.59809

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Oncogenes often promote cell death as well as proliferation. How oncogenes drive these diametrically opposed phenomena remains to be solved. A key question is whether cell death occurs as a response to aberrant proliferation signals or through a proliferation-independent mechanism. Here, we reveal that Src, the first identified oncogene, simultaneously drives cell proliferation and death in an obligatorily coupled manner through parallel MAPK pathways. The two MAPK pathways diverge from a lynchpin protein Slpr. A MAPK p38 drives proliferation whereas another MAPK JNK drives apoptosis independently of proliferation signals. Src-p38-induced proliferation is regulated by methionine-mediated Tor signaling. Reduction of dietary methionine uncouples the obligatory coupling of cell proliferation and death, suppressing tumorigenesis and tumor-induced lethality. Our findings provide an insight into how cells evolved to have a fail-safe mechanism that thwarts tumorigenesis by the oncogene Src. We also exemplify a diet-based approach to circumvent oncogenesis by exploiting the fail-safe mechanism.

【 授权许可】

CC BY