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This hypoxic environment in turn stabilizes HIF-1 in both cancer and stromal cells ( 4.4 Cancer associated fibroblasts Cancer-associated fibroblasts (CAFs) are among the most prevalent stromal cells in the breast cancer TME and have a pivotal role in the initiation, development, and resistance of cancer to therapies ( 4.5 Metabolic reprogramming and adipocyte crosstalk Metabolic reprogramming is one of the hallmarks of the breast cancer progression and is strongly influenced by the complex interactions among tumor cells and nearby adipocytes present within the TME ( 4.6 Extracellular vesicles and exosome-mediated signaling Extracellular vesicles (EVs), especially exosomes, plays a crucial role in mediating intercellular communications with the TME of breast cancer ( 4.7 Vascular niche and endothelial cell signaling In addition to angiogenesis, endothelial cells play an important role in the regulation of breast cancer progression by forming a vascular niche which promotes the survival, stemness, and metastatic spread of tumor cells ( 5 Mechanisms driving breast cancer For any type of cancer, including breast, the progression of the tumor is characterized by local recurrence, metastasis, and the development of therapy resistance, all of which pose a challenge that needs urgent attention

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Flipping the dogma - phosphatidylserine in non-apoptotic cell death