In summary, we here clarified a pivotal role of PKM2 acting as a non-metabolic function to promote the cancer cell progression in OSCC by translocating to the nucleus and subsequently inducing EMT and repressing TGIF2, and a new mechanism of TGIF2 regulation by PKM2 through a ubiquitin proteasome system in OSCC progression (Figure 7). The gene discussed is PKM; the disease is cancer.