Figure 2.

Lactagenesis is a highly orchestrated effort from oncogenes and tumor suppressor mutations for continuous glucose utilization to produce lactate involving five major steps: (i) increased glucose uptake through increased expression and translocation of glucose transporters GLUT by the transcription factors hypoxia-inducible factor 1 (HIF-1) and c-Myc oncogene as well as repression of tumor suppression factor p53 expression; (ii) increased glycolytic enzyme expression and activity, especially Lactate Dehydrogenase A (LDHA) by HIF-1, c-MYC and p53 downregulation; (iii) decreased mitochondrial function mainly by p53 dysregulation; (iv) increased lactate production, accumulation and release due to mass effect of accelerated glycolysis, mitochondrial dysfunction and increased LDHA expression and (v) Upregulation of monocarboxylate transporters MTC1 and MCT4 and their stabilizer, CD147, for lactate export and instigation of carcinogenesis in susceptible cancer candidate cells.