EGFRwt/vIII-PKM2-β-catenin cascade affects proliferation and chemo-sensitivity in head and neck squamous cell carcinoma

: Patients suffered from head and neck squamous cell carcinoma (HNSCC) have an overall poor prognosis owing to proliferation and resistance to treatment. Hence, mining the underlying mechanism of malignancies above and translating the bench outcomes to clinical practice are in urgent need. Previous studies found that the epidermal growth factor receptor (EGFR) increases and co-expresses with EGFRvIII in HNSCC tissues, which indicates poor prognosis of HNSCC patients. Here, we clarify that compared with EGFRwt, EGFRwt/vIII enhances the capability of proliferation and colony formation in HNSCC cells in vitro, and reduces the sensitivity to cisplatin. Furthermore, EGFRwt/vIII induces nuclear translocation of the M2 isoform of pyruvate kinase (PKM2) in a time-dependent manner. The aberrant expression of PKM2 in HNSCC suggests unfavorable outcome. Especially, nuclear PKM2 determines the activation of β-catenin signaling and regulates the proliferation and chemo-sensitivity of HNSCC cells. Together, our findings demonstrate that EGFRwt/vIII-PKM2-β-catenin cascade controls the proliferation and chemo-sensitivity of HNSCC, thereby providing a promising strategy for diagnosis and therapy of HNSCC.