# A pro-metastatic secretory pathway activated by p53 loss in lung cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $425,258

## Abstract

Cancer cells are embedded in a protective and nourishing “niche”, an
environment that cancer cells create by secreting proteins into their surroundings. Because cancer cells
depend on their niche to survive and spread to other parts of the body, we believe that therapies designed to
inhibit secretion could suppress cancer spread and thereby improve the length and quality of cancer patients'
lives. Developing such therapies will require a better understanding of how secretion is activated in cancer. Our
proposal will address this knowledge gap. Here we show that p53 protein loss, an established driver of cancer
spread, enhances secretion by reprogramming the Golgi apparatus, a master regulator of protein transport in
cells. We show that p53 loss activates the formation of a Golgi protein complex that controls secretion, and we
have identified secreted proteins that are essential for lung cancer growth and spread. Furthermore, we have
identified a drug that can block the formation of the Golgi protein complex, reduce secretion, and inhibit lung
cancer growth and spread. In this application, we seek to elucidate the molecular underpinnings and
therapeutic implications of the heightened secretion driven by p53 loss. In aim 1, we propose studies to
elucidate how the Golgi protein complex enhances secretion and drives lung cancer progression. In aim 2, we
propose studies to determine how the Golgi protein complex increases sensitivity to the drug we have
identified. These studies will provide insight into how secretion is activated in cancer and may lead to new
ways to target secretion in cancer patients.

## Key facts

- **NIH application ID:** 10440513
- **Project number:** 5R01CA255021-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Jonathan M Kurie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $425,258
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440513

## Citation

> US National Institutes of Health, RePORTER application 10440513, A pro-metastatic secretory pathway activated by p53 loss in lung cancer (5R01CA255021-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440513. Licensed CC0.

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