THESIS
2021
1 online resource (xxii, 170 pages) : illustrations (some color)
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 component...[
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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.
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