Abstract
Compared to normal cells, cancer cells have a unique metabolism by performing lactic acid fermentation in the presence of oxygen, also known as the Warburg effect. Researchers have proposed several hypotheses to elucidate the phenomenon, but the mechanism is still an enigma. In this review, we discuss three typical models, such as "damaged mitochondria", "adaptation to hypoxia", and "cell proliferation requirement", as well as contributions from mass spectrometry analysis toward our understanding of the Warburg effect. Mass spectrometry analysis supports the "adaptation to hypoxia" model that cancer cells are using quasi-anaerobic fermentation to reduce oxygen consumption in vivo. We further propose that hypoxia is an early event and it plays a crucial role in carcinoma initiation and development.