# Defining the role of Taiman, the Drosophila homolog of AIB1, as a super-competitor in developing epithelia

> **NIH NIH F31** · EMORY UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY
Invasive breast cancer is a deadly disease, killing ~42,000 women each year and costing the United States over
$16.5 billion annually. The complicated disease mechanisms that drive breast cancer are still insufficiently
understood to confidently design therapeutics. One mechanism emerging as a potential driver for local invasion
in breast and other cancers is ‘cell competition.’ This phenomenon occurs when two different cell populations
with different ‘fitness’ levels are juxtaposed in the same tissue. High fitness cells (called ‘winners’) grow more
rapidly and kill off slower growing neighbors (called ‘losers’) by apoptosis. Cancer cells acquire ‘winner’ status
by activating oncogenes. Oncogenes that confer ‘winner’ status are called ‘super-competitors.’ Our lab uses the
model organism, Drosophila melanogaster, to study conserved growth and proliferation pathways that are altered
in human cancer. In previous work we showed that Drosophila Taiman (Tai, AIB1 in humans), a co-activator of
the Ecdysone steroid hormone receptor (EcR), is a candidate super-competitor and imparts ‘winner’ status to
cells via production of the secreted, pro-apoptotic protein Spätzle (Spz), a Toll receptor ligand. We have also
shown that Tai binds the Yorkie (Yki) coactivator protein, the main target of the Hippo tumor suppressor pathway,
and that Yki:Tai collaboratively drive expression of pro-growth genes. However, we do not fully understand how
Tai drives neighbor killing, or whether it requires interactions with EcR and/or Yki. Moreover, classifying Tai as
a ‘super-competitor’ requires evidence that lowering the Tai dose confers ‘loser’ status relative to wildtype cells.
In the following three Aims, I will test my hypothesis that Tai acts as a super-competitor through either its
interaction with Yki (Hippo pathway) or EcR (ecdysone pathway), test the relative fitness of Tai-overexpressing
(Taihigh), wildtype (Taiwt), and Tai hypomorphic (Tailow) cells, and carry out experiments to identify cell competition
factors regulated by Tai. In Aim 1, I will assess the effects of elevated or reduced Tai on cell survival in homotypic
vs. heterotypic environments. To link to our published data, I will also investigate the requirement of the Spz/Toll
pathway in these contexts. In Aim 2, I will use candidate-based approaches to test the requirements for Yki/Hippo
and EcR signaling in Tai-driven killing of neighbor cells. Finally in Aim 3, I will use the unbiased, discovery-based
method Translating Ribosome Affinity Purification with sequencing (TRAP-Seq) to identify the Tai-induced
translated proteome in wing cells and candidate ‘competition’ factors within it. These aims will define the
molecular mechanisms underlying Tai-regulated cell competition in epithelial tissue. This work could also reveal
a link between cell competition and steroid hormone signaling, which could be a novel element of cancer biology.
The pathways that will be uncovered by this work will ha...

## Key facts

- **NIH application ID:** 10235192
- **Project number:** 1F31CA254207-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Colby Kristina Schweibenz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235192

## Citation

> US National Institutes of Health, RePORTER application 10235192, Defining the role of Taiman, the Drosophila homolog of AIB1, as a super-competitor in developing epithelia (1F31CA254207-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10235192. Licensed CC0.

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