# Project 1: The Acid Sphingomyelinase/Ceramide Kinase Pathway in Breast Cancer

> **NIH NIH P01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $207,754

## Abstract

PROJECT SUMMARY
 Bioactive sphingolipids constitute a family of related molecules with profound effects on key
cancer attributes. This proposal focuses specifically on heretofore unappreciated roles for an acid
sphingomyelinase (ASM)/ceramide kinase (CERK)-mediated pathway of sphingolipid metabolism
in regulating the formation of tumor cytokines and chemokines with roles in tumor inflammation
and invasion. Our recent published studies demonstrate that ASM-generated ceramide is coupled
to the action of CERK, resulting in the formation of ceramide 1-phosphate (C1P) with a key role
in mediating the specific production of chemokines (e.g. CCL5) and cytokines (e.g. IL6) in
response to TNF and IL1. Additional studies also disclose a key role for ASM and CERK in
regulating tumor cell invasion and metastasis. These results, coupled with the increased
appreciation of roles of TNF, IL1, CCL5 and IL6 in cancer inflammation and metastasis, have led
us to the hypothesis that this novel ASM/CERK/C1P pathway defines a previously unappreciated
mechanism regulating invasiveness and metastasis of breast cancer, with potentially important
roles in cancer metastasis. We will evaluate this hypothesis by pursuing the following specific
aims: 1.To define the roles and mechanisms by which the ASM/CERK/C1P pathway regulates
the production of inflammatory mediators. 2. To establish the role of CERK in cancer growth and
metastasis. 3. To advance CERK as a novel therapeutic target for breast cancer by solving its
structure. Taken together, these studies are key in not only defining novel pathways and
mechanisms of sphingolipid-mediated cancer biology at a molecular and cellular level, but also
for charting novel therapeutic potentials.
 The studies proposed in this project aim at defining how an enzyme of lipid (fat) metabolism
regulates some key functions of cancer cells that result in the production of factors that regulate
the ability of the tumor cells to migrate and invade which are critical for cancer metastasis.
Understanding these novel pathways and mechanisms not only enhances our understanding of
cancer behavior, but also promises to lead us to the identification of novel targets for developing
new inhibitors of cancer metastasis.

## Key facts

- **NIH application ID:** 10247631
- **Project number:** 5P01CA097132-18
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** YUSUF AWNI HANNUN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $207,754
- **Award type:** 5
- **Project period:** 2003-08-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247631

## Citation

> US National Institutes of Health, RePORTER application 10247631, Project 1: The Acid Sphingomyelinase/Ceramide Kinase Pathway in Breast Cancer (5P01CA097132-18). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247631. Licensed CC0.

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