# c-Myc Targets in the Pathogenesis of Human Cancers

> **NIH NIH R01** · WISTAR INSTITUTE · 2021 · $225,384

## Abstract

Project Summary
We have documented over the past several decades that MYC regulates genes that are involved in
glycolysis and glutaminolysis and other central metabolic pathways to achieve cell growth. However, these
studies were performed on a timescale that could not detect high frequency fluctuations in metabolite
concentrations, which could serve to synchronize interdependent biosynthetic processes to facilitate
building of biomass for cell growth and proliferation through their convergence. In preliminary studies, we
discovered through 2-hour interval time-series experiments that MYC induction resulted in ultradian (< 24 h
periods) oscillations of the concentrations of key intracellular metabolites, such as amino acids, while these
nutrients were being depleted from the medium. These observations uncover an intriguing, unsuspected
MYC-induced rapid metabolic oscillation (~6 h period) that we hypothesize to be essential for cancer cell
growth and proliferation. Moreover, our time-lapse studies of single hypoxic cells using a hypoxia-inducible
fluorescent reporter revealed intriguing cycling of hypoxia-inducible factor (HIF) activity with a ~4-5 h
period. High extracellular lactate concentrations increased the percentage of hypoxic cells that cycled HIF,
suggesting a potential single cell behavior similar to quorum sensing in stressed bacterial populations.
These short oscillatory periods are reminiscent of ultradian periods associated with p53-mdm2 activity (6-7
h period), Notch-Hes1 (2 h period), NFkB-IkB signaling (2 h period) and oscillations of glucocorticoid or
insulin secretion in vivo. Here we hypothesize that MYC induction of gene expression results in ultradian
metabolic oscillations that are essential for cancer cell growth and survival, permitting cells to undergo
phases of synchronous nutrient acquisition, respiration, and redox control with convergence of metabolic
pathways for biosynthesis. Understanding the mechanistic basis of these metabolic oscillations could lead
to new insights into cancer cell survival, revealing new therapeutic strategies. Hence, we set the following
Aims: Aim 1) Determine the role of MYC activation in oscillations of the metabolome. Aim 2) Determine the
role of MYC activation in oscillations of the cistrome, transcriptome, and proteome. Aim 3) Determine the
role of hypoxia in MYC-activated metabolic oscillations.

## Key facts

- **NIH application ID:** 10093977
- **Project number:** 5R01CA057341-29
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** CHI V. DANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,384
- **Award type:** 5
- **Project period:** 1992-09-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093977

## Citation

> US National Institutes of Health, RePORTER application 10093977, c-Myc Targets in the Pathogenesis of Human Cancers (5R01CA057341-29). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10093977. Licensed CC0.

---

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