Figure 1.

Molecular mechanisms supporting the proliferation of HCC cells despite serum withdrawal. In response to serum deprivation, HCC cells upregulate multiple enzymes involved in ketogenesis, resembling normal hepatocytes. In addition, serum-deprived HCC cells also upregulate OXCT1 expression, via a signal transduction pathway involving the sequential activation of mTORC2, AKT1 and SP1. Thus, contrary to normal hepatocytes, HCC cells also respond to serum deprivation by acquiring the ability to employ endogenous and exogenous ketone bodies for ATP synthesis. Such a capacity allows HCC cells to proliferate despite the nutritional stress imposed by serum withdrawal. TCA, tricyclic acid.