Investigation of JNK signaling pathway in a drosophila tumor model

Abstract

Tumorigenesis in mammals is proceeded by misregulation on various genes, which takes months to years. Further, the plasticity and evolving ability presented by mammalian tumors also provide difficulties for mechanism investigation. In Drosophila, mutation in genes encoding Scribble complex proteins induce neoplastic tumor formation, which models many aspects of mammalian tumorigenesis. However, the cellular and molecular basis of how fly tumors develop is still largely unknown. By means of bulk RNA sequencing analysis and biochemical experiments, we found that JNK signaling activity is required for growth regulation of scrib mutant tumors. Further, single-cell RNA sequencing analysis and genetic screening of potential JNK targets revealed that myosin II and JAK-STAT signaling components are also required for growth regulation. Primary study on molecular mechanisms suggested that myosin II components potentially regulate JNK activity via a positive feedback loop. On the other hand, immune pathways, including JAK-STAT pathway, Toll, and IMD pathway, might regulate tumor growth in another unknown mechanism. Furthermore, pathway enrichment analysis and genetic results demonstrated that elevation of Yki and ERK activity would enhance scrib mutant tumor growth as well. Notably, JNK activity would repress ERK activity. Collectively, those results suggested that activation of JNK pathway would regulate various downstream targets to fuel tumor growth regulation.

Date of Award	2021
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Yan YAN (Supervisor)