The role of “aerobic glycolysis” in cancer has been examined often in the past. Results from those studies, most of which were performed on two dimensional conditions (2D, tissue culture plastic), demonstrate that aerobic glycolysis occurs as a consequence of oncogenic events. These oncogenic events often drive malignant cell growth and survival. Although 2D based experiments are useful in elucidating the molecular mechanisms of oncogenesis, they fail to take contributions of the extracellular microenvironment into account. Indeed we, and others, have shown that the cellular microenvironment is essential in regulating processes that induce and/or suppress the malignant phenotype/properties. This regulation between the cell and its microenvironment is both dynamic and reciprocal and involves the integration of cellular signaling networks in the right context. Therefore, given our previous demonstration of the effect of the microenvironment including tissue architecture and media composition on gene expression and the integration of signaling events observed in three-dimension (3D), we hypothesized that glucose uptake and metabolism must also be essential components of the tissue's signal “integration plan” – that is, if uptake and metabolism of glucose were hyperactivated, the canonical oncogenic pathways should also be similarly activated. This hypothesis, if proven true, suggests that direct inhibition of glucose metabolism in cancer cells should either suppress or revert the malignant phenotype in 3D. Here, we review the up-to-date progress that has been made towards understanding the role that glucose metabolism plays in oncogenesis and re-establishing basally polarized acini in malignant human breast cells.

过去经常检查“有氧糖酵解”在癌症中的作用。这些研究的结果，其中大部分是在二维条件下进行的（2D，组织培养塑料），表明有氧糖酵解是致癌事件的结果。这些致癌事件通常会驱动恶性细胞的生长和存活。尽管基于 2D 的实验可用于阐明肿瘤发生的分子机制，但它们未能将细胞外微环境的贡献考虑在内。事实上，我们和其他人已经表明，细胞微环境在调节诱导和/或抑制恶性表型/特性的过程中是必不可少的。细胞与其微环境之间的这种调节既是动态的又是相互的，并且涉及在正确的环境中整合细胞信号网络。因此，鉴于我们先前证明了微环境的影响，包括组织结构和培养基组成对基因表达的影响以及在三维 (3D) 中观察到的信号事件的整合，我们假设葡萄糖摄取和代谢也必须是微环境的重要组成部分。组织的信号“整合计划”——也就是说，如果葡萄糖的摄取和代谢被过度激活，典型的致癌途径也应该被类似地激活。这一假设如果被证明是正确的，则表明直接抑制癌细胞中的葡萄糖代谢应该抑制或恢复 3D 中的恶性表型。这里，