Loss of STARD7 Triggers Metabolic Reprogramming and Cell Cycle Arrest in Breast Cancer

Area of Science:

• Cell Biology
• Cancer Metabolism
• Molecular Oncology

Background:

• Cancer cells exhibit metabolic reprogramming to fuel proliferation.
• Mitochondrial function depends on lipid transfer from the endoplasmic reticulum (ER).
• Metabolic reprogramming and cell cycle progression links are underexplored in cancer.

Purpose of the Study:

• Investigate the role of STARD7, a lipid transfer protein upregulated in breast cancer, in metabolic reprogramming and cell cycle control.
• Elucidate the functional consequences of STARD7 deficiency in breast cancer cells.

Main Methods:

• Analysis of STARD7 expression in breast cancer.
• Metabolomic profiling to identify accumulating metabolites upon STARD7 loss.
• Epigenetic analysis (H3K27 trimethylation) of cell cycle-related genes.
• Assessment of cell cycle progression and proliferation assays.
• Evaluation of ERα and EGFR signaling pathways.

Main Results:

• STARD7 loss induces metabolic reprogramming with carnitine derivatives and S-Adenosyl-L-methionine (SAM) accumulation.
• Elevated SAM levels increase H3K27 trimethylation on cell cycle gene promoters.
• STARD7 deficiency leads to cell cycle arrest and impaired ERα-dependent proliferation.
• EGFR signaling is dysregulated in triple-negative breast cancer cells lacking STARD7 due to altered lysosomal trafficking.

Conclusions:

• STARD7 is crucial for maintaining mitochondrial function and supporting cell cycle progression in breast cancer.
• STARD7 deficiency disrupts metabolic homeostasis, leading to epigenetic alterations that inhibit proliferation.
• Targeting STARD7 or its downstream pathways may offer therapeutic strategies for breast cancer.