Reprogramming of energetic metabolism: increased expression and roles of pyruvate carboxylase in papillary thyroid cancer.

BACKGROUND: Energetic metabolism is described to be deregulated in cancer and the Warburg effect is presented as a major hallmark. Recently, cellular heterogeneity in tumors and tumor microenvironment have been recognized to play an important role in several metabolic pathways in cancer. However, their contribution to papillary thyroid cancer (PTC) development and metabolism is still poorly described.

METHODS: We performed a proteomic analysis of 5 PTC and investigated the cellular distribution of several upregulated metabolic proteins in the cancer and in the stromal cells of PTC.

RESULTS: MS/MS analysis revealed the upregulation of many metabolism-related proteins, among which pyruvate carboxylase. Pyruvate carboxylase knockdown in thyroid cell lines alters their proliferative and motility capacities, and measurements of oxygen consumption rates showed that this enzyme is involved in the replenishment of the TCA cycle. Immunostainings of several upregulated metabolic proteins showed that thyroid cancer cells have an increased mitochondrial oxidative metabolism compared to stromal cells.

CONCLUSION: PTC have a very active TCA cycle, continuously replenished by a pyruvate carboxylase mediated anaplerosis. This is specifically observed in the tumor cells.