Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008 China; Cancer Research Institute, Key Laboratory of Carcinogenesis, Ministry of Health, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078 China.
Institute of Medical Sciences, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008 China.
Cancer Lett. 2018 May 28;422:81-93. doi: 10.1016/j.canlet.2018.02.028. Epub 2018 Feb 23.
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.
放射治疗已成为癌症患者治疗的重要手段，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 CSCs 的放射抵抗的分子机制在很大程度上仍难以捉摸。在这里，我们发现辐射抗性（IR）细胞表现出增强的干细胞样特性，同时具有增强的锚定非依赖性生长和转移能力。EGFR 不仅导致辐射抗性亚系中子宫内膜癌干细胞标志物的获得增加，而且对癌症干细胞表型和致瘤性至关重要。此外，PKM2 作为 EGFR 的相互作用伙伴，在 IR 细胞中诱导 EMT 表型和干细胞样特性。最后，我们发现 EGFR-PKM2 轴的调节功能依赖于核 EGFR。总之，我们的研究表明，EGFR 和 PKM2 直接相互作用并结合在一起，调节与干性相关基因的转录，促进干细胞样表型，从而促进侵袭和转移。
