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Updated: Jul 9, 2025

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
Published on: March 14, 2021
Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast
Zheqiong Tan1,2, Pragney Deme3, Keerti Boyapati1
1Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Background:
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and leads to the poorest patient outcomes despite surgery and chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead to the development of novel molecular targets are critically important for improving therapeutic options for treating TNBC.
Methods:
We sought to identify novel therapeutic targets in TNBC by combining genomic and functional studies with lipidomic analysis, which included mechanistic studies to elucidate the pathways that tie lipid profile to critical cancer cell properties. Our studies were performed in a large panel of human breast cancer cell lines and patient samples.
Results:
Comprehensive lipid profiling revealed that phospholipid metabolism is reprogrammed in TNBC cells. We discovered that patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC cell lines and tissues from breast cancer patients. Silencing of PNPLA8 disrupted phospholipid metabolic reprogramming in TNBC, particularly affecting the levels of phosphatidylglycerol (PG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and glycerophosphocholine (GPC). We showed that PNPLA8 is essential in regulating cell viability, migration and antioxidation in TNBC cells and promoted arachidonic acid and eicosanoid production, which in turn activated PI3K/Akt/Gsk3β and MAPK signaling.
Conclusions:
Our study highlights PNPLA8 as key regulator of phospholipid metabolic reprogramming and malignant phenotypes in TNBC, which could be further developed as a novel molecular treatment target.
Insights
Researchers identified patatin-like phospholipase domain-containing lipase 8 (PNPLA8) as a key driver in triple-negative breast cancer (TNBC). Targeting PNPLA8 could offer new therapeutic strategies for this aggressive cancer subtype.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with poor patient outcomes.
- Current treatments including surgery and chemotherapy are often insufficient for TNBC.
- Novel molecular targets are crucial for improving TNBC therapeutic options.
Purpose of the Study:
- To identify novel therapeutic targets for TNBC.
- To investigate the role of lipid metabolism in TNBC progression.
- To combine genomic, functional, and lipidomic analyses.
Main Methods:
- Utilized a large panel of human breast cancer cell lines and patient samples.
- Performed comprehensive lipid profiling to analyze metabolic reprogramming.
- Conducted mechanistic studies to link lipid profiles to cancer cell properties.
Main Results:
- Phospholipid metabolism is reprogrammed in TNBC cells.
- Patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC.
- PNPLA8 silencing disrupted phospholipid metabolism and affected cell viability, migration, and antioxidation.
Conclusions:
- PNPLA8 is a key regulator of phospholipid metabolic reprogramming in TNBC.
- PNPLA8 influences malignant phenotypes including cell viability and migration.
- PNPLA8 represents a potential novel molecular treatment target for TNBC.
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