# Propionate metabolism as an essential metabolic adaptation for tumor progression

> **NIH NIH R00** · H. LEE MOFFITT CANCER CTR & RES INST · 2022 · $249,000

## Abstract

PROJECT SUMMARY/ ABSTRACT
The current understanding of how primary tumor cells acquire the capacity to metastasize is still very limited.
This becomes a major problem to find effective cures for all types of cancer, as metastatic disease accounts
for the majority of cancer-related mortality. Therefore, a deep understanding of the changes that occur in
primary tumor cells that lead them to acquire the ability to escape the immune system, migrate, invade,
colonize and survive at distant niches is necessary. Metabolic reprogramming is at the intersection of signaling
pathways and their ability to elicit cellular changes to promote increased cell survival, growth and proliferation.
However, which metabolic adaptations are necessary to enable cancer cells to create a permissive
microenvironment and survive the arduous process that leads to metastases remains poorly understood.
Here, I propose that increased propionate metabolism is an essential metabolic adaptation that drives tumor
progression and ultimately leads to metastasis. My preliminary data show that not only is increased propionate
metabolism crucial for the acquisition of metastatic properties, but also that metastatic breast cancer cells are
“addicted” to this pathway. Therefore, my goal is to understand how pathways that drive metastasis regulate
propionate metabolism and what functions increased propionate metabolism has during tumor progression.
During the K99 phase of this award, I will determine the molecular mechanisms that regulate propionate
metabolism and will evaluate if propionate metabolism affects metastasis formation in vivo. During the R00
phase of this award, I will focus on understanding what key functional roles propionate metabolism serves to
support tumor progression and the development of metastases. This work will establish a new branch of
metabolic signaling and expand our understanding of metabolic dependencies and their role during tumor
progression. In addition to the scientific goals of this proposal, I have also proposed a comprehensive training
plan during the K99 phase of the award that will prepare me for the transition to independence. This includes
guidance from three renowned mentors, Drs. John Blenis, Lewis Cantley and Douglas Fearon, acquisition of
new skills in immunology and the study of tumor microenvironment, training on state-of-the-art technology for
isotope tracing, and development of professional skills to guide my transition to independence.

## Key facts

- **NIH application ID:** 10457486
- **Project number:** 5R00CA218686-05
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Ana da silva Gomes
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2020-09-10 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457486

## Citation

> US National Institutes of Health, RePORTER application 10457486, Propionate metabolism as an essential metabolic adaptation for tumor progression (5R00CA218686-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10457486. Licensed CC0.

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