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

机译:核EGFR-PKM2轴诱导抗抗性细胞中的癌症干细胞样特性

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摘要

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. (C) 2018 Elsevier B.V. All rights reserved.
机译:放射治疗已成为治疗癌症患者的重要工具,但大多数患者在5年内复发。复发是由于存在癌症干细胞(CSCs),但CSC中的辐射敏感度的分子机制仍然很大程度上是难以捉摸的。这里,我们发现抗辐射(IR)细胞与升高的锚固型生长和转移能力一起表现出升高的干细胞样特性。 EGFR不仅导致增加肠胃瘤中子宫内膜癌干细胞标志物的增加,对于癌症干细胞表型和致瘤性是至关重要的。此外,PKM2用作EGFR的相互作用伴侣,其在IR细胞中诱导EMT表型和干细胞状性质。最后,我们发现EGFR-PKM2轴的调节功能取决于核EGFR。总之,我们的研究表明,EGFR和PKM2彼此直接相互作用并结合,以调节茎秆相关基因的转录并促进干燥的表型,从而促进侵袭和转移。 (c)2018 Elsevier B.v.保留所有权利。

著录项

  • 来源
    《Cancer letters》 |2018年第2018期|共13页
  • 作者单位

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Inst Med Sci 87 Xiangya Rd Changsha 410008 Hunan Peoples R China;

    Cent S Univ Xiangya Hosp 2 Dept Thorac Surg Changsha Hunan Peoples R China;

    Cent S Univ Xiangya Hosp Dept Pathol Changsha 410008 Hunan Peoples R China;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Changzhi Med Coll Dept Pathophysiol Changzhi 046000 Shanxi Peoples R China;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

    Cent S Univ Xiangya Hosp Minist Educ Key Lab Carcinogenesis &

    Canc Invas 87 Xiangya Rd;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

    Radioresistance; EGFR; PKM2; Stem-like; Metastasis;

    机译:辐射探测器;EGFR;PKM2;茎状;转移;

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