Conclusively, these results suggest that PAK2 depletion affects c-Myc–PKM2 expression and compromises the HNC cell energy metabolism; however, the rescue of Warburg effect upon complementation of c-Myc in PAK2-depleted cells indicates that PAK2–c-Myc–PKM2 axis plays an important role in cancer metabolism and thereby HNC development. The gene discussed is PKM; the disease is cancer.