Extensive studies have been reported the non-canonical functions of pyruvate kinase M2 (PKM2) as a kinase, transcriptional regulator, and even cell-to-cell communicator, emphasizing its importance in various signaling pathways. However, the role of secreted PKM2 in cancer progression and its signaling pathway is yet to be elucidated. In this study, we found that extracellular PKM2 enhanced the migration of low-metastatic, benign colon cancer cells by upregulating claudin-1 expression and internalizing it to the cytoplasm and nucleus. Knock-down of claudin-1 significantly reduced extracellular PKM2-induced cell migration. Inhibition of either protein kinase C (PKC) or epidermal growth factor receptor (EGFR) resulted in a reduction of extracellular PKM2-mediated claudin-1 expression, suggesting EGFR-PKC-claudin-1 as a signaling pathway in the extracellular PKM2-mediated tumorigenesis of colon cancer cells.

中文翻译：

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细胞外丙酮酸激酶 M2 通过上调结肠癌细胞中的claudin-1 表达来促进细胞迁移。


广泛的研究报道了丙酮酸激酶 M2 (PKM2) 作为激酶、转录调节因子甚至细胞间通讯器的非典型功能，强调了其在各种信号传导途径中的重要性。然而，分泌型 PKM2 在癌症进展中的作用及其信号通路尚未阐明。在这项研究中，我们发现细胞外PKM2通过上调claudin-1表达并将其内化到细胞质和细胞核来增强低转移良性结肠癌细胞的迁移。 Claudin-1 的敲低显着减少了细胞外 PKM2 诱导的细胞迁移。抑制蛋白激酶 C (PKC) 或表皮生长因子受体 (EGFR) 会导致细胞外 PKM2 介导的claudin-1 表达减少，表明 EGFR-PKC-claudin-1 作为细胞外 PKM2 介导的肿瘤发生中的信号通路结肠癌细胞。