Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, China.
Sci Rep. 2017 Jun 6;7(1):2886. doi: 10.1038/s41598-017-03031-1.
Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro. Subcutaneous xenografts and pulmonary metastases models were constructed in nude mice to compare the differences in tumorgenesis and metastasis after Knockdown of PKM2. Our results obtained from in vitro cell biological behavior, in vivo tumorigenicity studies, and primary GC samples revealed an oncogenic role for PKM2 in GC. Furthermore, for those GC patients who received radical resection, PKM2 might serve as a novel prognostic biomarker and target which would allow for a brand new treatment strategy for GC in the clinical settings.
丙酮酸激酶 M2（PKM2）是糖酵解的关键激酶，是所有增殖细胞的特征。PKM2 在胃癌（GC）中的作用仍然不明确，需要进一步确定。为了更好地了解 PKM2 在 GC 细胞迁移和侵袭中的作用，我们使用 qRT-PCR 和 Western blot 检测了 GC 细胞系中 PKM2 的表达。通过免疫组织化学方法在包含 88 例 GC 患者的队列中分析了 PKM2 的预后价值。我们使用短发夹 RNA 质粒载体在 NCI-N87 和 BGC-823 细胞中敲低 PKM2，并在体外研究其生物学行为和下游信号通路。在裸鼠中构建皮下异种移植和肺转移模型，比较敲低 PKM2 后肿瘤发生和转移的差异。我们从体外细胞生物学行为、体内肿瘤发生研究和原发性 GC 样本中获得的结果表明，PKM2 在 GC 中具有致癌作用。此外，对于接受根治性切除术的 GC 患者，PKM2 可能成为一种新的预后生物标志物和靶点，为 GC 的临床治疗提供一种全新的治疗策略。
