# GRM1-induced HIF-1α and reprogramming of glutamine metabolisms in melanoma

> **NIH VA I01** · VA NEW JERSEY HEALTH CARE SYSTEM · 2020 · —

## Abstract

A new emerging hallmark for many malignancies is altered metabolic direction to
support rapid cell proliferation. Considerable progress has been made in elucidating
how modified cell signaling contributes to deregulated cell growth in cancer, much less
is known regarding metabolic rewiring to provide for the demand in building blocks to
support the ever-increasing cell numbers. Within the last few years metabolite profiling
between normal and cancer cells has provided new insights to uncover the underlying
mechanisms of cellular transformation. Glutamine is the most abundant amino acid in
blood and is recognized as a critical contributor in nearly every central metabolic task of
proliferating tumor cells. Recently, glutamine was deemed as an essential component
in mitochondrial metabolisms to ensure that rapidly growing tumor cells will remain
metabolically versatile, particularly the reprogramming of the oxidative to reductive
mitochondrial glutamine metabolism. Reductive glutamine metabolism has been shown
to be preferred under hypoxia condition via the stabilization of the hypoxia-induced
transcription factor 1 (HIF-1).
Our group demonstrated the etiological role of an ectopic expression of a murine
neuronal receptor, metabotropic glutamate receptor 1 (GRM1) in mouse melanocytes
in genetically modified transgenic mouse melanoma models. Aberrant expression of
the human form of GRM1 was also observed in 65% of human melanoma cell lines
and biopsy samples but not normal human melanocytes, suggesting its involvement in
melanomagenesis. Recently, we uncovered yet another consequence in cells with
enhanced/aberrant GRM1 expression, upregulated HIF-1. These preliminary results
suggest there may be a link between altered glutamine metabolism and glutamatergic
signaling mediated by aberrant GRM1 expression. We hypothesize that ectopic GRM1
expression in melanocytes results in deregulated cell proliferation, increase in HIF-1,
which participates in the rewiring of the metabolic networks that fuel the increasing
demand for the synthesis of biological molecules required for cell growth.

## Key facts

- **NIH application ID:** 9815448
- **Project number:** 5I01BX003742-03
- **Recipient organization:** VA NEW JERSEY HEALTH CARE SYSTEM
- **Principal Investigator:** Suzie Chen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815448

## Citation

> US National Institutes of Health, RePORTER application 9815448, GRM1-induced HIF-1α and reprogramming of glutamine metabolisms in melanoma (5I01BX003742-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9815448. Licensed CC0.

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