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During breast cancer progression, upregulated GPR81 is activated by extracellular lactate, which leads to PI3K/Akt pathway stimulation and the regulation of cell survival. Activation of the PI3K/Akt-CREB pathway results in increased AREG production, which AREG promotes neo-vessel formation (angiogenesis) in tumor endothelial cells and also provides a proliferative advantage to cancer cells and tumor growth.
