Scientists report that an evolutionarily conserved transcription factor may have both positive and negative effects on the growth of tumors, depending on whether or not the tumor cells have enough oxygen.
The research, published by Cell Press in the December 28th issue of Molecular Cell, provides critical new information about how normal cells and cancer cells survive under stress.
Dividing tumor cells are often deprived of oxygen as a result of their rapid expansion or aberrant blood vessels. Response to stressful low oxygen conditions, known as hypoxia, involves expression of several genes that enable cells to adapt to the oxygen deficit. This response is primarily mediated by the hypoxia-inducible transcription factors, HIF1 and HIF2.
HIF proteins play a key role in hypoxic tumor development and are often associated with poor patient prognosis. Hypoxic tumor cells exhibit decreased sensitivity to radiation and chemotherapy, and increased potential for invasion and metastasis. Interestingly, recent research findings have also revealed an anti-cancer role for HIF1 that is mediated by the initiation of programmed cell death, called apoptosis, in response to severe hypoxic stress. Although HIF1 has been linked to several pro-apoptotic target genes, specific mechanisms that regulate this particular function of HIF1 are not well understood.