Nuclear EGFR-PKM2 axis induces cancer stem cell-like characteristics in irradiation-resistant cells

Release time:2020-07-13

Impact Factor:7.36

Affiliation of Author(s):中南大学

Journal:Cancer Lett

Key Words:EGFR; Metastasis; PKM2; Radioresistance; Stem-like

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.

Co-author:Liu N, Lai W, Yan B, Chen L, Liu S, Liu S, Wang X, Xiao D, Liu X, Mao C, Jiang Y, Jia J, Liu Y, Yang R, Cao Y

First Author:Shi Y

Indexed by:Journal paper

Correspondence Author:Tao Y

Volume:422

Page Number:81-93

Translation or Not:no

Date of Publication:2018-05-28

Included Journals:SCI