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

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Shi Y,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,Tao Y

doi

10.1016/j.canlet.2018.02.028

subject

Has Abstract

pub_date

2018-05-28 00:00:00

pages

81-93

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(18)30161-7

journal_volume

422

pub_type

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