Nuclear EGFR-PKM2 axis induces cancer stem cell-like characteristics in irradiation-resistant cells. (28th May 2018) - Shi, Ying
Abstract: Radiation therapy has become an important tool in the treatment of cancer patients, but most patients relapse within 5 years. Relapse is due to the presence of cancer stem cells (CSCs), but the molecular mechanism of radioresistance in CSCs remains largely elusive. Here, we found that irradiation-resistant (IR) cells exhibited increased stem cell-like properties together with elevated anchorage-independent growth and metastasis ability. EGFR not only leads to increased acquisition of endometrial cancer stem cell markers in radioresistant sublines but is critical for the cancer stem-cell phenotype and tumorigenicity. Moreover, PKM2 functions as an interacting partner of EGFR, which induces the EMT phenotype and stem cell-like properties in IR cells. Finally, we found that the regulatory function of the EGFR-PKM2 axis is dependent on nuclear EGFR. In sum, our study indicated that EGFR and PKM2 directly interact and bind with each other to regulate the transcription of stemness-related genes and promote the stem-like phenotype, thus promoting invasion and metastasis. Highlights: The EGFR and PKM2 complex facilitates radioresistance in an EGFR dependent manner. Depletion of EGFR diminishes stem-like properties through reducing PKM2 binding to stemness gene promoters. Targeting the nuclear intact complex of EGFR and PKM2 overcomes radioresistence in cancer.