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

Authors :
Hiroshi Nishida
Morihiro Okada
Lynna Yang
Tomomi Takano
Sho Tabata
Tomoyoshi Soga
Diana M Ho
Jongkyeong Chung
Yasuhiro Minami
Sa Kan Yoo
Source :
eLife, Vol 10 (2021)
Publication Year :
2021
Publisher :
eLife Sciences Publications Ltd, 2021.

Abstract

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.

Details

Language :
English
ISSN :
2050084X
Volume :
10
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.1b064bcba1664a949429a82dd3418f4f
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.59809