“Hippo’s Dynamic Duo”: How Wg and Yki Orchestrate Tumor Growth?

“Hippo’s Dynamic Duo”: How Wg and Yki Orchestrate Tumor Growth?"

Presenter(s)

Arushi Rai

Comments

11:00-12:30, Kennedy Union 222

Description

Studies with Drosophila Ras V12 ,scrib -/- tumor models reveal that Yorkie, a Hippo pathway effector, interacts with other signaling pathways to form a dynamic network in cancer cells. In these models, Wingless (Wg) acts upstream of Caspases, JNK, and Yki, regulating tumor growth and development (Waghmare et al. 2024). We hypothesize that Yorkie is the key downstream regulator of this network. Heterozygosity of yki (yki B5 /+; Ras V12 ,scrib -/- ) reduced tumor clone size compared to Ras V12 ,scrib -/- clones, showing effects on survival (low Diap1 expression and change in apoptotic response). Wg is ectopically induced in Ras V12 and Ras V12 ,scrib -/- clones. Wg acts upstream of this network, and is also Yorkie's transcriptional target. We tested the interaction between Yki and Wg and found that downregulating Wg signaling (dTCF DN ; Ras V12 ,scrib -/- ) also reduced tumor clone size. Downregulating Wg pathway in Ras V12 ,scrib -/- resulted in decreased DIAP1 intensity (survival) when compared to Ras V12 ,scrib -/- tumor clones. To further explore how Wg and Yki promote tumor growth, we created double mutants combining loss of yki (yki B5-/- ) and dominant-negative dTCF to downregulate Wg signaling in Ras V12 ,scrib -/- clones (dTCF DN yki B5 ;Ras V12 ,scrib -/- ). We have investigated the synergistic effects of double mutants on (a) hallmarks of cancer such as invasion, cell adhesion, and survival signaling by immunohistochemistry-based approach (b) the transcriptional network of Ras V12 ,scrib -/- tumor clones by analyzing the mRNA expression by qRT-PCR. Here, we present our progress on the organization of the molecular network that involves Wingless and Yorkie.

Publication Date

4-23-2025

Project Designation

Graduate Research

Primary Advisor

Madhuri Kango-Singh, Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship; Traditions; Practical Wisdom

“Hippo’s Dynamic Duo”: How Wg and Yki Orchestrate Tumor Growth?

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