HIF1A and carcinoma: Here, given the results of our metabolomics study of metastatic melanoma in the context of a review of current literature, we suggest that the accumulation of fumarate plays an important role both in TCA cycle and HIF signal pathway shown in Figure 8, where it further inhibits the PHDs and hence activates the HIF-1α to promote carcinoma cell proliferation, angiogenesis and metastases.