# Investigating the effect of SARS-CoV-2 infection on metabolic reprogramming in lung cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $140,227

## Abstract

PROJECT SUMMARY/ABSTRACT
Metabolic reprogramming with aerobic glycolysis is a hallmark of cancer. We have previously shown that
glucose transporter expression evolves during lung carcinogenesis, with pre-malignant and early-stage lesions
relying on sodium-glucose transporter 2 (SGLT2) and advanced cancers switching to GLUT1-mediated
diffusion. Our parent R01 project is focused on the hypothesis that heterogeneity of glucose transport reflects
heterogeneous metabolic and biological phenotypes: SGLT2 is associated with mitochondrial metabolism and
slow proliferation in early lesions, GLUT1 with glycolytic metabolism and fast growth in advanced, poorly
differentiated cancers. Early lesions of the lung adenocarcinoma spectrum are slow growing and can take
years to progress, or may never progress, to invasive cancer. This indolent behavior correlates with absence of
GLUT1 and expression of SGLT2. The molecular events that drive the switch from SGLT2-positive indolent
lesions to GLUT1-positive aggressive cancers are unknown; we are testing the hypothesis that metabolic
reprogramming and GLUT1 upregulation play a driving role in this progression.
Pulmonary viral infections cause atypical pneumonia, characterized by interstitial inflammation and low
metabolic activity as measured by positron emission tomography with the tracer FDG, which detects GLUT1
activity. However, intensely FDG-avid lesions have been observed incidentally in asymptomatic patients who
then resulted positive for SARS-CoV-2 infection. The absence of systemic or local symptoms suggests that the
high FDG uptake is not due in these cases to massive inflammatory responses, but to increased glucose
uptake by alveolar epithelial cells infected by SARS-CoV-2. Viral infections can cause metabolic
reprogramming in the host epithelial cells similar to the Warburg effect described for cancer, and this
reprogramming is required for viral replication.
Here, we will investigate in vitro and in vivo the hypotheses that 1) SARS-CoV-2 infection in alveolar epithelial
cells induces metabolic reprogramming with increased glycolysis and intensely positive FDG uptake; 2) if this
metabolic reprogramming is induced in pre-malignant lesions of the lung adenocarcinoma spectrum, the virus-
induced switch from SGLT2-driven mitochondrial metabolism to GLUT1-associated glycolysis accelerates the
progression of early-stage, indolent lesions to aggressive, poorly differentiated and invasive cancers.

## Key facts

- **NIH application ID:** 10199384
- **Project number:** 3R01CA237401-01A1S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Claudio Scafoglio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $140,227
- **Award type:** 3
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199384

## Citation

> US National Institutes of Health, RePORTER application 10199384, Investigating the effect of SARS-CoV-2 infection on metabolic reprogramming in lung cancer (3R01CA237401-01A1S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199384. Licensed CC0.

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