Respiratory Medicine, Yan'an University Affiliated Hospital, Yan'an 716000, China.
Nursing Department, Yan'an University Affiliated Hospital, Yan'an 716000, China.
Biosci Rep. 2019 May 14;39(5). doi: 10.1042/BSR20182099. Print 2019 May 31.
Pyruvate dehydrogenase kinase-1 (PDK-1), a gatekeeper enzyme, was involved in cancer progression, such as tumor angiogenesis, cell survival, and growth. Recent evidence indicated that PDK-1 may be involved in lung cancer, however, the function and underlying mechanism of PDK-1 is remaining unclear. In the present study, our aim was to investigate the role and mechanisms of PDK-1 in human non-small cell lung cancer (NSCLC) cells. We first observed that PDK-1 was highly expressed in NSCLC cell lines. PDK-1 silence resulted in the inhibition of NSCLC cell survival. Also, cell apoptosis and caspase-3 activity were increased by PDK-1 knockdown in H1299 and A549 cells. Attenuation of PDK-1 expression blocked YAP and insulin receptor substrate 2 (IRS2) expression, and PDK-1 silence suppressed IRS2 expression dependent on Hippo-YAP signaling pathway. Moreover, further studies confirmed that YAP or IRS2 overexpression reversed the action of PDK-1 in NSCLC cells. In conclusion, our findings indicate that PDK1/Hippo-YAP/IRS2 signaling pathway plays a critical role in NSCLC cell survival and apoptosis.
丙酮酸脱氢酶激酶 1（PDK-1）作为一种关键酶，参与了癌症的进展，如肿瘤血管生成、细胞存活和生长。最近的证据表明，PDK-1 可能与肺癌有关，但 PDK-1 的功能和潜在机制尚不清楚。在本研究中，我们的目的是研究 PDK-1 在人类非小细胞肺癌（NSCLC）细胞中的作用和机制。我们首先观察到 PDK-1 在 NSCLC 细胞系中高表达。PDK-1 沉默导致 NSCLC 细胞存活受到抑制。此外，在 H1299 和 A549 细胞中敲低 PDK-1 会增加细胞凋亡和半胱天冬酶-3 活性。抑制 PDK-1 表达会阻断 YAP 和胰岛素受体底物 2（IRS2）的表达，并且 PDK-1 沉默依赖 Hippo-YAP 信号通路抑制 IRS2 表达。此外，进一步的研究证实，YAP 或 IRS2 的过表达逆转了 PDK-1 在 NSCLC 细胞中的作用。总之，我们的研究结果表明，PDK1/Hippo-YAP/IRS2 信号通路在 NSCLC 细胞存活和凋亡中发挥着关键作用。
