Guo Chang-Ying, Yan Chen, Luo Lan, Goto Shinji, Urata Yoshishige, Xu Jian-Jun, Wen Xiao-Ming, Kuang Yu-Kang, Tou Fang-Fang, Li Tao-Sheng
Department of Thoracic Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Stem Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
Oncol Rep. 2017 Apr;37(4):2161-2166. doi: 10.3892/or.2017.5438. Epub 2017 Feb 10.
Cancer cells express the M2 isoform of glycolytic enzyme pyruvate kinase (PKM2) for favoring the survival under a hypoxic condition. Considering the relative low oxygen microenvironment in stem cell niche, we hypothesized that an enhanced PKM2 expression associates with the biological properties of cancer stem cells. We used A549 human lung cancer cell line and surgical resected lung cancer tissue samples from patients for experiments. We confirmed the co-localization of PKM2 and CD44, a popular marker for cancer stem cells in lung cancer tissue samples from patients. The expression of PKM2 was clearly observed in approximately 80% of the A549 human lung cancer cells. Remarkably, enhanced expression of PKM2 was specially observed in these cells that also positively expressed CD44. Downregulation of PKM2 in CD44+ cancer stem cells by siRNA significantly impaired the potency for spheroid formation, decreased the cell survival under fetal bovine serum deprivation and hypoxic conditions, but increased their sensitivity to anti-cancer drug of cisplatin and γ-ray. The enhanced expression of PKM2 seems to associate with the biological properties of cancer stem cells from A549 human lung cancer cells. Selective targeting of PKM2 may provide a new strategy for cancer therapy, especially for patients with therapeutic resistance.
癌细胞表达糖酵解酶丙酮酸激酶（PKM2）的M2亚型，以利于在缺氧条件下存活。考虑到干细胞微环境中相对低氧的微环境，我们推测PKM2表达增强与癌症干细胞的生物学特性相关。我们使用A549人肺癌细胞系和患者手术切除的肺癌组织样本进行实验。我们证实了PKM2与CD44在患者肺癌组织样本中共同定位，CD44是肺癌中癌症干细胞的常用标志物。在大约80%的A549人肺癌细胞中明显观察到PKM2的表达。值得注意的是，在这些也阳性表达CD44的细胞中特别观察到PKM2表达增强。通过siRNA下调CD44+癌症干细胞中的PKM2显著损害了球体形成能力，降低了胎牛血清剥夺和缺氧条件下的细胞存活率，但增加了它们对顺铂和γ射线抗癌药物的敏感性。PKM2表达增强似乎与A549人肺癌细胞中癌症干细胞的生物学特性相关。选择性靶向PKM2可能为癌症治疗提供一种新策略，特别是对于具有治疗抗性的患者。
