Investigating the Role of Complex I Loss in Thyroid Tumorigenesis

Changes in cellular metabolism are considered one of the hallmarks of cancer. In 1924, Otto Warburg initially posited that defects in cellular respiration drive tumorigenesis after observing that tumor cells often perform aerobic glycolysis in culture. Since then, multiple studies have demonstrated that most tumors actually require intact cellular respiration for proliferation. However, cancers of the colon, kidney, and thyroid are enriched in loss-of-function mutations predicted to negatively impact respiration. A recent study has shown that a cohort of tall cell variant-papillary thyroid cancer (TCV-PTC) tumors demonstrate widespread loss of Complex I of the electron transport chain. TCV-PTC is a clinically aggressive form of papillary thyroid cancer, driven universally by the BRAF V600E activating mutation. I have developed a murine model of Braf-driven thyroid cancer to investigate the role of Complex I loss in both tumor initiation and progression.