# Hexokinase 2 and cancer therapy

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $545,313

## Abstract

Cancer cells are metabolically different from normal matching cells, and this is manifested by the
high rate of glucose metabolism in cancer cells. The high rate of glucose metabolism in cancer
cells is, at least in part, due to the marked induction of hexokinase (HK2) expression, which is
not expressed in most normal cells. Most normal adult tissues and cells express hexokinase 1
(HK1), but when they convert into cancer cells, they start expressing high levels HK2. Thus, HK2
could be a hallmark of cancer cells and could be targeted for cancer therapy. Over the years we
provided genetic proofs of concept that HK2 can be systemically deleted in mice to inhibit cancer
without adverse consequences. We showed that HK2 deficiency inhibited both initiation and
maintenance of cancer in mouse models of lung cancer, breast cancer, liver cancer, and prostate
cancer. Likewise, inducible knockdown of HK2 in human cancer cells inhibited the growth of
tumors after tumor formation. In this grant application we will investigate novel HK2 activities that
were not previously explored. These activities include: (i) A novel moonlighting function of HK2,
independently of its glucose kinase activity. This activity could determine the stability of certain
proteins such as MCL1, NRF2, and SNAIL that are associated with cell survival, redox regulation,
and EMT and metastasis respectively. (ii) A role of HK2 in glycosylation, tumor microenvironment
and immunotherapy. (iii) The effect of HK2 on gene expression through histone lactylation.

## Key facts

- **NIH application ID:** 10875294
- **Project number:** 5R01CA258299-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Nissim Hay
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $545,313
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875294

## Citation

> US National Institutes of Health, RePORTER application 10875294, Hexokinase 2 and cancer therapy (5R01CA258299-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10875294. Licensed CC0.

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