Further extending this paradigm, the “reverse Warburg effect” describes a stromal-epithelial coupling where cancer-associated fibroblasts (CAFs), under oxidative stress, activate hypoxia-inducible factor 1-alpha (HIF-1α) and release lactate via MCT4, which cancer cells then import via MCT1 to fuel their oxidative metabolism, creating an acidic, lactate-rich niche that supports tumor growth [59]. Here, HIF1A is linked to neoplasm.