# Intercepting novel functions of AURKA in gastric tumorigenesis

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $422,099

## Abstract

ABSTRACT/SUMMARY
Gastric carcinoma (GAC) is the third most common cause of cancer-related death world-wide, causing more
than 700,000 deaths each year. Unfortunately, the majority of gastric cancer patients are diagnosed at a late
stage (Stage III or IV) in the United States, with a poor response to therapy and five-year survival rate of 5.2%.
Infection with Helicobacter pylori (H. pylori), a type I carcinogen, is the main risk factor for gastric
carcinogenesis. Infection with H. pylori creates a unique environment where epithelial cells must adapt to
chronic cellular stress and are forced develop adaptive survival fitness properties that not only promote
tumorigenesis but also resistance to chemotherapeutics. Understanding the molecular functions of
carcinogenic biological factors such as H. pylori infection is a key step for developing evidence-based
therapeutic approaches that are founded on the biology and molecular underpinning of gastric carcinogenesis.
We have found that Aurora kinase A (AURKA) is a critical target at the 20q amplicon, overexpressed in
approximately 60% of gastric cancers. We identified novel functions of AURKA in promoting EIF4E and cap-
dependent translation of critical genes such as SOX9 and LGR5 that promote survival and expansion of
tumorigenic cells in response to infection. We have also found that treatment-resistant cells were enriched for
high levels of AURKA, SOX9, and LGR5. This proposal has three specific aims that include mechanistic,
functional, and translational studies using unique in vitro and in vivo models, including organoid cultures and
mouse models. In aim 1, we will investigate the mechanistic role of AURKA in reprogramming the translational
machinery in response to infection with H. pylori. We will determine the AURKA-dependent functions in
promoting gastric tumorigenesis and resistance to therapy, using in vivo models in Aim 2. The translational
significance of our findings and therapeutic efficacy of targeting AURKA will be investigated in Aim 3. Upon
completion of this work, we expect to unveil a new paradigm of cross-talk between AURKA and EIF4E-
dependent translational machinery in promoting gastric tumorigenesis and resistance to therapy.

## Key facts

- **NIH application ID:** 10899451
- **Project number:** 5R01CA266528-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** WAEL EL-RIFAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $422,099
- **Award type:** 5
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899451

## Citation

> US National Institutes of Health, RePORTER application 10899451, Intercepting novel functions of AURKA in gastric tumorigenesis (5R01CA266528-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10899451. Licensed CC0.

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