# MNSOD ACETYLATION PROMOTES CANCER STEM CELL PHENOTYPES IN BREAST CANCER

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $125,592

## Abstract

PROJECT SUMMARY
Aggressive phenotypes of breast cancer are characterized by increased capacity of evading immune
surveillance and generating metastasis. Our groups recently described that metastatic breast cancer cells
expressing high levels of acetylated superoxide dismutase 2 (SOD2K68Ac) accumulate mitochondria-derived
reactive oxygen species (mtROS) and promote stabilization of hypoxia-inducible factor 2α (HIF2α), involved
tumor aggressiveness. HIF2α also regulates genes associated with immune protection, including the
programmed death-ligand 1 (PDL1) that is widely recognized as a molecule eliciting immune evasion in cancer
cells. Hence, we propose to investigate (1) if accumulation of SOD2K68Ac promotes PDL1 upregulation via HIF2α
in breast cancer cells; (2) if SOD2K68Ac/HIF2α promotes mammary cancer immune evasion and metastasis in
vivo using mouse model; and (3) if there is a subgroup of women with breast cancer that exhibits
SOD2K68Ac/HIF2α molecular signature correlating with high PDL1 expression and immunotherapy resistance. We
expect to identify a new mechanism of cancer immune evasion that can be targeted to improve therapeutic
approaches to treat aggressive phenotypes of breast cancer exhibiting SOD2K68Ac molecular signature. The
proposed translational research will be conducted by Dr. Coelho under the mentorship of Dr. Marcelo Bonini
(primary mentor), Dr. Leonidas Platanias (co-mentor) and Dr. Massimo Cristofanilli (clinical co-mentor). All
mentors have exemplary records of scientific achievement, innovation and leadership in the translational pipeline
of cancer therapeutics and diagnostics. In addition to the scientific goal of this application, we expect that Dr.
Coelho will accomplish a multidisciplinary training in clinical research, leadership, writing and management
essential to establish an independent career in cancer immunobiology.

## Key facts

- **NIH application ID:** 10380372
- **Project number:** 3R01CA216882-04S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Marcelo G. Bonini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $125,592
- **Award type:** 3
- **Project period:** 2018-08-14 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380372

## Citation

> US National Institutes of Health, RePORTER application 10380372, MNSOD ACETYLATION PROMOTES CANCER STEM CELL PHENOTYPES IN BREAST CANCER (3R01CA216882-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380372. Licensed CC0.

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