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Understanding the Role of Lipid Metabolism in Epithelial-Mesenchymal Plasticity in Breast Cancers

Principal Investigator: Anushka Dongre

Co-PI: Glenn Simmons

Department of Biomedical Sciences
Sponsor: Cornell Adam and Rachel Broder Fund for Cancer Research
Title: Understanding the Role of Lipid Metabolism in Epithelial-Mesenchymal Plasticity in Breast Cancers
Project Amount: $25,000
Project Period: August 2025 to July 2026

DESCRIPTION (provided by applicant):

The majority of breast cancer-associated deaths are attributed to the metastatic spread of the disease to distant sites. The spread of disease is potentiated by activating the epithelial-mesenchymal plasticity (EMP), which drives resistance to chemotherapies and immunotherapies. Additionally, dysregulated lipid metabolism in cancer cells promotes invasion and cellular motility. In fact, murine mesenchymal breast cancer cells have decreased levels of unsaturated fatty acid relative to their epithelial counterparts, implying a correlative relationship between the EMP program and lipid metabolism. However, whether altered lipid metabolism promotes metastasis by influencing the residence of cancer cells in the epithelial or mesenchymal plastic states requires further investigation.


Moreover, whether modulating the lipidomic profile of breast cancer cells can enhance their responsiveness to anti-cancer therapies remains to be established. We propose that inhibition of unsaturated fatty acids promotes metastasis by activating an EMP program in breast cancer cells. Additionally, preserving these unsaturated fatty acids will likely enhance responses to conventional chemotherapy by altering cellular plasticity. These objectives will be addressed by combining novel in-vitro assays utilizing three-dimensional organoids and in vivo pre-clinical murine models of primary breast tumors, spontaneous metastasis, and experimental metastasis. The outcomes of the proposed work will uncover how lipid metabolism regulates metastatic colonization. A significant impact is in advancing our understanding of the most effective strategies to harness lipid signaling to sensitize refractory breast tumors to therapy.