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Updated: Feb 20, 2026
Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
Published on: July 3, 2025
Decrypting the PAK4 transcriptome profile in mammary tumor forming cells using Next Generation Sequencing
Chetan K Rane1, Misaal Patel2, Li Cai2
1Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, United States.
Abstract:
The p-21 Activated Kinase 4 (PAK4) protein kinase is implicated in many cancers, including breast cancer. Overexpression of PAK4 is sufficient to cause mouse mammary epithelial cells (iMMECs) to become tumorigenic. To gain insight into the long-term gene expression changes that occur downstream to PAK4, we performed Next Generation Sequencing of RNA collected from PAK4 overexpressing iMMECs and wild-type iMMECs. We identified a list of genes whose expression levels were altered in response to PAK4 overexpression in iMMECs. Some of these genes, including FoxC2 and ParvB, are consistent with a role for PAK4 in cancer. In addition, PAK4 regulates many genes that are frequently associated with the inflammatory response, raising the possibility that there is a connection between PAK4, inflammation, and the tumor microenvironment. This study delineates the PAK4 transcriptome profile in transformed mammary cells and can provide translational utility in other types of cancers as well.
Insights
p-21 Activated Kinase 4 (PAK4) overexpression drives mammary cell tumorigenesis. PAK4 alters gene expression, including cancer-related genes and those linked to inflammation, impacting the tumor microenvironment.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- p-21 Activated Kinase 4 (PAK4) is a protein kinase implicated in various cancers, including breast cancer.
- PAK4 overexpression is sufficient to induce tumorigenicity in mouse mammary epithelial cells (iMMECs).
Purpose of the Study:
- To investigate the long-term gene expression changes downstream of PAK4.
- To delineate the PAK4 transcriptome profile in transformed mammary cells.
Main Methods:
- Next Generation Sequencing (NGS) of RNA from PAK4-overexpressing and wild-type iMMECs.
- Comparative analysis of gene expression profiles.
Main Results:
- Identified a list of genes with altered expression due to PAK4 overexpression.
- Observed changes in genes like FoxC2 and ParvB, consistent with PAK4's role in cancer.
- Found that PAK4 regulates genes associated with the inflammatory response.
Conclusions:
- PAK4 plays a significant role in mammary cell transformation and tumorigenesis.
- PAK4-mediated gene expression changes suggest a link between PAK4, inflammation, and the tumor microenvironment.
- The PAK4 transcriptome profile offers potential translational utility for other cancer types.
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