# StarD5, a protein that translocates cholesterol to the plasma membrane, is a novel target for Colon Cancer

> **NIH VA I01** · VA VETERANS ADMINISTRATION HOSPITAL · 2022 · —

## Abstract

Colorectal cancer (CRC) is the third leading cause of cancer death in the US. It is difficult to cure CRC
because majority of the existing therapies fail to significantly obliterate seeds of cancer called `cancer stem
cells (CRCSCs). Cellular cholesterol metabolism is a single most important target for CRCSCs. However,
existing therapies that target this pathway, e.g. statins fail to significantly inhibit cholesterol levels in the cells
due to redundant mechanisms that govern cholesterol levels in cancer cells. However, cholesterol utilization is
regulated by select group of specific cholesterol transport proteins, which if targeted, can have critical effect on
plasma membrane (PM) biophysical properties of CRC cells. We have identified a cholesterol transport protein
called StarD5, which is the only known mammalian protein that regulates cholesterol transport to cell
membrane. StarD5 is significantly overexpressed in human colon cancer tissues and particularly in colon
CRCSCs. Inhibition of StarD5 resulted in significant inhibition of colon CSCs in vitro and in vivo, as well as
cholesterol contents in PM resulting in increased PM fluidity and robust inhibition of Insulin-like growth factor-1
receptor (IGF1R) and epidermal growth factor receptor (EGFR) signaling. We propose to examine, in detail,
the significance of StarD5 overexpression on colon cancer initiation, progression, and patient outcomes
as well as impact of StarD5 modulation on CRCSC phenotype in human CRCSCs (Aim 1). We would
also like to understand mechanisms of how StarD5 inhibition regulates CSCs. To that end, we propose to
determine the effect of StarD5 inhibition on PM fluidity, influx of platinum agents, and growth factor signaling
initiated in PM (Aim 2). Moreover, we plan to examine the efficacy of small molecular inhibitors of StarD5
(SD5i) on CRCSC phenotype using primary human colon spheroids as well as determine their efficacy of in
combination with FDA-approved chemotherapy and targeted therapy (panitumumab) against advanced
animal models of CSCs (Aim 3). The studies will provide novel insight into how alternation in
membrane cholesterol regulates cancer growth, and provide a novel class of target for cancer therapies
that may lead to long-term remission and/or cure by targeting therapy resistant CRCSCs.

## Key facts

- **NIH application ID:** 10456014
- **Project number:** 5I01BX000837-11
- **Recipient organization:** VA VETERANS ADMINISTRATION HOSPITAL
- **Principal Investigator:** Bhaumik B Patel
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2011-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456014

## Citation

> US National Institutes of Health, RePORTER application 10456014, StarD5, a protein that translocates cholesterol to the plasma membrane, is a novel target for Colon Cancer (5I01BX000837-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10456014. Licensed CC0.

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