# Tumor Cell Dependence on Host Metabolism

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $454,038

## Abstract

ABSTRACT
Rapid fermentation of glucose to lactate (the “Warburg effect”) was the first molecular characteristic assigned
to cancer. Recent years have seen an explosion of interest in the metabolic capabilities of tumor cells,
including up-regulated anabolism, redox defense, and alternative routes of nutrient acquisition such as
macropinocytosis and autophagy. While these cellular capabilities play a critical role, metabolically, tumors
ultimately depend on circulating nutrients provided by the host. The extent to which tumors generate
energy and biomass building blocks from a few preferred circulating nutrients like glucose, versus uptake
diverse nutrients to minimize their own biosynthetic work, remains, however, poorly understood. For example,
many tumors upregulate serine biosynthesis. At the same time, tumor growth is sensitive to dietary serine
intake. Which contributes more—circulating serine from the diet or serine synthesized in the tumor?
While substantial efforts have been made to understand the essential metabolic pathways within tumor cells,
comparatively little effort has gone into understanding the tumor's dependency on host metabolism. We have
surprisingly observed that consumption of circulating nutrients by tumors is profoundly different from
that of cultured cancer cells. We have also surprisingly observed that host autophagy is important for
sustaining circulating nutrients and for the growth of implanted tumors (where autophagy remains
intact). These findings highlight the potential for host metabolic processes to impact tumor growth. What are
the critical circulating nutrients for tumors? How is host metabolism altered by autophagy deficiency? Which
are the critical changes that impair tumor growth? More broadly, how can tumor dependency on host
metabolism be exploited therapeutically? To address these questions, we will employ state-of-the-art isotope
tracer techniques to murine tumor models of lung cancer and melanoma. Specifically, we will address the role
of host metabolism in mouse models of K-Ras lung cancer, and B-Raf lung cancer and melanoma:
Aim 1: Identify the contributions of circulating nutrients and internal tumor metabolic pathways to lung
cancer and melanoma growth. We hypothesize that, rather than using glucose and glutamine as their
primary substrates, tumors in vivo consume a broad diversity of circulating nutrients, including amino acids,
fats, and lactate, thereby minimizing biosynthetic requirements and enhancing metabolic robustness.
Aim 2: Determine the mechanism underlying dependence of tumors on host autophagy. We hypothesize
that host autophagy is required to maintain circulating nutrients to support tumor growth.
Aim 3: Assess the therapeutic potential of modulating circulating metabolites. We hypothesize that
decreasing circulating levels of nutrients including arginine, methionine, and glycine will have anti-tumor
activity.

## Key facts

- **NIH application ID:** 10192670
- **Project number:** 5R01CA163591-10
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** JOSHUA D RABINOWITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $454,038
- **Award type:** 5
- **Project period:** 2012-08-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192670

## Citation

> US National Institutes of Health, RePORTER application 10192670, Tumor Cell Dependence on Host Metabolism (5R01CA163591-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10192670. Licensed CC0.

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