PP6 Disruption Synergizes with Oncogenic Ras to Promote JNK-Dependent Tumor Growth and Invasion

Xianjue Ma, Jin Yu Lu, Yongli Dong, Daming Li, Juan N. Malagon, Tian Xu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

RAS genes are frequently mutated in cancers, yet an effective treatment has not been developed, partly because of an incomplete understanding of signaling within Ras-related tumors. To address this, we performed a genetic screen in Drosophila, aiming to find mutations that cooperate with oncogenic Ras (RasV12) to induce tumor overgrowth and invasion. We identified fiery mountain (fmt), a regulatory subunit of the protein phosphatase 6 (PP6) complex, as a tumor suppressor that synergizes with RasV12 to drive c-Jun N-terminal kinase (JNK)-dependent tumor growth and invasiveness. We show that Fmt negatively regulates JNK upstream of dTAK1. We further demonstrate that disruption of PpV, the catalytic subunit of PP6, mimics fmt loss-of-function-induced tumorigenesis. Finally, Fmt synergizes with PpV to inhibit JNK-dependent tumor progression. Our data here further highlight the power of Drosophila as a model system to unravel molecular mechanisms that may be relevant to human cancer biology.

Original languageEnglish (US)
Pages (from-to)2657-2664
Number of pages8
JournalCell Reports
Volume19
Issue number13
DOIs
StatePublished - Jun 27 2017
Externally publishedYes

Keywords

  • Drosophila
  • Fmt
  • JNK
  • PpV
  • Ras
  • tumorigenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'PP6 Disruption Synergizes with Oncogenic Ras to Promote JNK-Dependent Tumor Growth and Invasion'. Together they form a unique fingerprint.

Cite this