Polarity protein Canoe mediates overproliferation via modulation of JNK, Ras-MAPK and Hippo signalling

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.