Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
Department of Pathology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
Mol Oncol. 2021 Feb;15(2):560-578. doi: 10.1002/1878-0261.12843. Epub 2020 Dec 11.
Recent studies revealed the role of dynamin-related protein 1 (DRP1), encoded by the DNM1L gene, in regulating the growth of cancer cells of various origins. However, the regulation, function, and clinical significance of DRP1 remain undetermined in lung adenocarcinoma. Our study shows that the expression and activation of DRP1 are significantly correlated with proliferation and disease extent, as well as an increased risk of postoperative recurrence in stage I to stage IIIA lung adenocarcinoma. Loss of DRP1 in lung adenocarcinoma cell lines leads to an altered mitochondrial morphology, fewer copies of mitochondrial DNA, decreased respiratory complexes, and impaired oxidative phosphorylation. Additionally, the proliferation and invasion are both suppressed in DRP1-depleted lung adenocarcinoma cell lines. Our data further revealed that DRP1 activation through serine 616 phosphorylation is regulated by ERK/AKT and CDK2 in lung adenocarcinoma cell lines. Collectively, we propose the multikinase framework in activating DRP1 in lung adenocarcinoma to promote the malignant properties. Biomarkers related to mitochondrial reprogramming, such as DRP1, can be used to evaluate the risk of postoperative recurrence in early-stage lung adenocarcinoma.
最近的研究揭示了动力相关蛋白 1（DRP1）的作用，该蛋白由 DNM1L 基因编码，在调节各种起源的癌细胞生长中发挥作用。然而，DRP1 在肺腺癌中的调节、功能和临床意义仍未确定。我们的研究表明，DRP1 的表达和激活与增殖和疾病程度显著相关，并且在 I 期至 IIIA 期肺腺癌中增加了术后复发的风险。肺腺癌细胞系中 DRP1 的缺失会导致线粒体形态改变、线粒体 DNA 拷贝数减少、呼吸复合物减少和氧化磷酸化受损。此外，DRP1 耗尽的肺腺癌细胞系的增殖和侵袭均受到抑制。我们的数据还进一步表明，DRP1 通过丝氨酸 616 磷酸化的激活受到 ERK/AKT 和 CDK2 在肺腺癌细胞系中的调节。总之，我们提出了在肺腺癌中激活 DRP1 以促进恶性特性的多激酶框架。与线粒体重编程相关的生物标志物，如 DRP1，可以用于评估早期肺腺癌术后复发的风险。
