Yorkie dependent transcriptional network promotes tumor growth.

Yorkie dependent transcriptional network promotes tumor growth.

Presenter(s)

Arushi Rai

Comments

Presentation: 1:15 p.m.-2:30 p.m., Kennedy Union Ballroom

Additional authors:
Arushi Rai1, Indrayani Waghmare1,3, Amit Singh1, 2, Madhuri Kango-Singh1, 2

1: Department of Biology, University of Dayton, Dayton, OH
2: Integrative Science and Engineering Center, Dayton, OH
3: Cell and Developmental Biology, Vanderbilt University, Nashville, TN

Description

Studies in Drosophila and other tumor models have revealed cancer promoting signaling interactions and transcriptional addictions in tumors cells. The Hippo pathway effector, Yorkie (Yki) is a key mediator of such interactions and presents an attractive opportunity to study transcriptional dependencies in cancer cells. The RasV12 scrib-/- tumor mosaic model is well-established and shows activation of oncogenic Ras in the background of impaired apical-basal polarity. This model is widely used study molecular mechanisms and signaling events downstream of the oncogenic Ras and Ras-mediated Yorkie (Yki) activation in RasV12, scrib-/- tumor cells. Previously, we have shown that in RasV12, scrib-/- cells Wingless (Wg), Caspases (e.g., the initiator caspase Dronc) and JNK are activated to promote tumorigenesis through their non-apoptotic roles. Amongst these, Wg/Wnt pathway is known to act via canonical and non-canonical pathways during development and cancer, and interact with Yki to promote cancer growth. Genetic epistasis showed that Wg acts upstream of Caspases, JNK and Yki, and downregulation of Wg reduced tumor growth by downregulation of Caspases, JNK and Yki reporters. Our goal is to further understand how the two evolutionarily conserved signaling pathways i.e., Hippo and Wingless crosstalk and interact with each other to regulate tumor growth. To understand this intricate wiring of Wingless-Yorkie during tumor growth and invasion, we will use the RasV12, scrib-/- tumor model in Drosophila imaginal discs. Preliminary data showed that wg transcriptional reporters are upregulated in RasV12, scrib-/- cells, suggesting that increased accumulation of Wg may be due to increased transcription. In other contexts, wg is shown as a transcriptional target of Yki. Therefore, we will test for (a) the effects of Yorkie protein, the main effector molecule of Hippo pathway, on wg transcription and expression of other Wg pathway components by reporter assays, and qRT-PCR- based approaches, and (b) feedback interactions that promote tumorigenesis using genetic epistasis-, and immunohistochemistry-based approaches. Here, we present our progress on the organization of the molecular network involving Wingless and Yorkie.

Publication Date

4-20-2022

Project Designation

Graduate Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium project, College of Arts and Sciences

United Nations Sustainable Development Goals

Good Health and Well-Being

Yorkie dependent transcriptional network promotes tumor growth.

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