Nuclear EGFR-PKM2 axis induces cancer stem cell-like characteristics in irradiation-resistant cells. (28th May 2018)

• Record Type: Journal Article
• Authors: Shi, Ying; Liu, Na; Lai, Weiwei; Yan, Bin; Chen, Ling; Liu, Shouping; Liu, Shuang; Wang, Xiang; Xiao, Desheng; Liu, Xiaoli; Mao, Chao; Jiang, Yiqun; Jia, Jiantao; Liu, Yating; Yang, Rui; Cao, Ya; Tao, Yongguang
• Is Part Of: Cancer letters. Volume 422(2018)
• Page Start: 81
• Page End: 93
• Publication Date: 2018-05-28
• Subjects: Radioresistance -- EGFR -- PKM2 -- Stem-like -- Metastasis; CSCs cancer stem cells -- SLCCs stem-like cancer cells -- P parental -- IR irradiation-resistant -- EGFR epidermal growth factor receptor -- PKM2 pyruvate kinase M2 -- PEP phosphoenolpyruvate -- ADP adenosine diphosphate -- ATP adenosine-triphosphate -- EMT epithelial-to-mesenchymal transition -- ABCG2 ATP-binding cassette sub-family G member 2 -- KLF4 Kruppel-like factor-4 -- Oct4 octamer-binding transcription factor-4 -- Sox2 SRY (sex determining region Y)-box 2 -- ALDH1 aldehyde dehydrogenase 1 -- STAT3 signal transducer and activator of transcription 3 -- FGFR1 fibroblast growth factor receptor 1 -- DMEM Dulbecco's modified Eagle's medium -- RT-qPCR reverse transcription-polymerase chain reaction -- IHC immunohistochemistry -- ISH in situ hybridization -- DAB diaminobenzidine -- ChIP chromatin immunoprecipitation -- RNAi RNA interference -- FITC fluorescein isothiocyanate -- PI propidium iodide -- SP side population -- bFGF basic fibroblast growth factor -- DEAB N, N-diethylaminobenzaldehyde -- TIF2 the nuclear receptor coactivator 2 -- RHA RNA helicase A -- PAR poly-ADP-ribose -- JMJD5 Jumonji C domain-containing dioxygenase 5 -- HSP90 heat-shock protein 90 -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- CXCR4 C-X-C chemokine receptor type 4 -- MMP9 matrix metallopeptidase 9; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.02.028
• Languages: English
• ISSNs: 0304-3835

Abstract

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.