RRC ID 54143
著者 Ma Z, Li P, Hu X, Song H.
タイトル Polarity protein Canoe mediates overproliferation via modulation of JNK, Ras-MAPK and Hippo signalling.
ジャーナル Cell Prolif
Abstract OBJECTIVES:Over the past decade an intriguing connection between cell polarity and tumorigenesis has emerged. Multiple core components of the junction complexes that help to form and maintain cell polarity display both pro- and anti-tumorigenic functions in a context-dependent manner, with the underlying mechanisms poorly understood.
MATERIALS AND METHODS:With transgenic fly lines that overexpress or knock down specific signalling components, we perform genetic analysis to investigate the precise role of the polarity protein Canoe (Cno) in tumorigenesis and the downstream pathways.
RESULTS:We show that overexpression of cno simultaneously activates JNK and Ras-MEK-ERK signalling, resulting in mixed phenotypes of both overproliferation and cell death in the Drosophila wing disc. Moderate alleviation of JNK activation eliminates the effect of Cno on cell death, leading to organ overgrowth and cell migration that mimic the formation and invasion of tumours. In addition, we find that the Hippo pathway acts downstream of JNK and Ras signalling to mediate the effect of Cno on cell proliferation.
CONCLUSIONS:Our work reveals an oncogenic role of Cno and creates a new type of Drosophila tumour model for cancer research.
巻・号 52(1)
ページ e12529
公開日 2019-1-1
DOI 10.1111/cpr.12529
PMID 30328653
PMC PMC6430484
MeSH Animals Carcinogenesis / genetics Cell Death / genetics Cell Polarity / physiology* Cell Proliferation / genetics Drosophila / embryology Drosophila / genetics Drosophila / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Gene Knockdown Techniques Intracellular Signaling Peptides and Proteins / metabolism* JNK Mitogen-Activated Protein Kinases / metabolism* Neoplasms / genetics Neoplasms / pathology Protein Serine-Threonine Kinases / metabolism* Wings, Animal / embryology ras Proteins / metabolism*
IF 5.753
引用数 3
リソース情報
ショウジョウバエ 2534R-3