# Investigating the Roles and Regulation of FOXO Transcription Factors in GBM and basal breast cancer

> **NIH NIH SC3** · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2020 · $108,975

## Abstract

PROJECT SUMMARY:
This proposal examines newly identified cellular roles for FOXO transcription factors in regulating stem cell-
related gene expression and signal transduction in cancer. The phosphatidylinositol 3 kinase (PI3K) pathway is
almost universally mutated to an activate state in cancer to drive growth and survival. Partially redundant,
evolutionarily conserved FOXO -1, -3 and -4 transcription factors are best known for hindering cell cycle
progression and inducing apoptosis on the PI3K pathway. Canonically, PI3K indirectly inactivates FOXO factors.
However, we found FOXO factors in the nucleus of PI3K-activated cancer cell lines such as U87MGs and
BT549s, suggesting novel regulation and roles for these factors in these settings. Other researchers have found
FOXO factors in the nucleus in contexts with activated PI3K (embryonic stem cells and DLBCL). To address the
role of FOXO factors in PI3K-activated cancers such as U87MG, we utilized an innovative approach (CRISPR,
corroborated with RNAi and overexpression studies). Our preliminary evidence indicated that FOXO3 disruption
reduced the expression of stem cell-related genes in U87MGs such as OCT4 and SOX2, whereas exogenous
FOXO3 induced these genes. Aim 1 will identify mechanisms that promote FOXO nuclear localization in these
novel contexts. Aim 2 will define precise molecular mechanisms that are utilized by FOXO factors to induce the
expression of stem cell-related genes in PI3K-activated cancers such as U87MG and BT549 cells. These aims
will be accomplished by employing qRT-PCR, western blot analyses, chromatin immuno-precipitation analyses,
genomics approaches and confocal microscopy. The impact of FOXO factors on stem cell gene expression and
signal transduction has broad ramifications to prevalent human diseases such as cancer, neurodegeneration,
diabetes and aging. Proposed studies and research enhancement objectives will be conducted at the second
largest Hispanic-serving Institution in the United States, the University of Texas Rio Grande Valley (UTRGV),
which has not been a major recipient of NIH support. Funding and completion of these studies will increase
research capabilities at UTRGV, which serves over 27,000 students who are 89% Hispanic thereby serving the
mission of the SCORE Program.

## Key facts

- **NIH application ID:** 9883816
- **Project number:** 5SC3GM132053-02
- **Recipient organization:** UNIVERSITY OF TEXAS RIO GRANDE VALLEY
- **Principal Investigator:** Megan E Keniry
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $108,975
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883816

## Citation

> US National Institutes of Health, RePORTER application 9883816, Investigating the Roles and Regulation of FOXO Transcription Factors in GBM and basal breast cancer (5SC3GM132053-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9883816. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*