# The role of cholesterol biosynthesis in metastatic and recurrent endometrial cancer

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $254,927

## Abstract

Endometrial cancer is the most common gynecologic malignancy, with an estimated 66,570 new cases in 2021.
Although early-stage and low grade endometrial cancer generally exhibits a favorable prognosis, metastatic
and recurrent endometrial cancer is incurable with currently available standard therapies for most women.
Therefore, there is an urgent obligation to explore the mechanism of tumor metastasis and recurrence to
further elucidate the progression of endometrial cancer. We have developed a genetically engineered mouse
model for metastatic and recurrent endometrial cancer that implicates coexistent Pten and Mig-6 mutations in
endometrial cancer. Pten mutation is not sufficient for distant metastasis, but mice with concurrent ablation of
Mig-6 and Pten develop distant metastasis. After hysterectomy at stage I of endometrial cancer in mutant mice
with deficiency of Pten and Mig-6, the double mutant mice developed recurrence of endometrial cancer in the
abdomen and lung. Our preliminary results show that the expression of genes related to cholesterol
biosynthesis pathway was significantly increased in the mutant mice. Based upon these results, we
hypothesize that MIG-6 suppresses metastasis and recurrence in endometrial cancer with PTEN
mutation by inhibiting cholesterol biosynthesis. Our Specific Aims are directed at understanding: 1) the
tumorigenic effects of MIG-6 loss in recurrence of endometrial cancer with PTEN mutation; 2) the molecular
signature of primary tumor, circulating tumor cells, and recurrent tumor in the mutant mice; and 3) the ability of
statins to prevent recurrence in endometrial cancer. There is strong innovation in the novelty of our hypotheses
and cutting-edge technical approaches. In particular, we will employ the first preclinical animal model that
closely resembles human endometrial cancer with distant metastasis and recurrence.

## Key facts

- **NIH application ID:** 10467152
- **Project number:** 1R01CA264944-01A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Jae-Wook Jeong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $254,927
- **Award type:** 1
- **Project period:** 2022-02-02 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10467152

## Citation

> US National Institutes of Health, RePORTER application 10467152, The role of cholesterol biosynthesis in metastatic and recurrent endometrial cancer (1R01CA264944-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10467152. Licensed CC0.

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