具有 BRAFV600E 突变的甲状腺乳头状癌 (PTC) 与较差的预后相关。由于新出现的耐药性，BRAF 抑制剂的疗效可能有限。瓦尔堡效应可能具有癌症治疗意义。目前尚不清楚 BRAFV600E 突变是否与 PTC 中的葡萄糖代谢改变有关。本研究检查了 BRAFV600E 和 DRP1 对 PTC 细胞中各种细胞过程的影响，包括：细胞增殖、迁移、侵袭、线粒体裂变、葡萄糖代谢、活性氧 (ROS) 的产生和细胞凋亡。我们使用 RT-qPCR 评估甲状腺癌组织中关键糖酵解酶的表达。此外，通过蛋白质印迹和免疫组织化学染色研究了 BRAFV600E 和 DRP1 之间的调控相互作用。我们进一步评估了 DRP1 对 PTC 的影响以及 Dabrafenib 和 2-DG 的体外和体内抑制作用。我们发现 BRAFV600E 突变显着增强了 PTC 中的有氧糖酵解，同时抑制了氧化磷酸化。我们确定 BRAFV600E/p-ERK/p-DRP1(Ser616) 信号通路是 PTC 进展的关键介质。 BRAFV600E/p-ERK/p-DRP1(Ser616) 信号通路通过上调 HK2 表达从而增加有氧糖酵解来增强细胞增殖。其次，它通过促进线粒体裂变和降低ROS水平来抑制细胞凋亡。此外，我们证明2-DG和Dabrafenib的联合治疗可显着阻碍BRAFV600E阳性PTC的进展。BRAFV600E/p-ERK/p-DRP1(Ser616)信号通路在葡萄糖代谢重编程中发挥着关键作用，有助于BRAFV600E 阳性 PTC 的侵袭性和进展。我们的研究结果表明，使用 2-DG 和 Dabrafenib 的联合治疗方法有可能改善 BRAFV600E PTC 患者的预后。

Papillary thyroid cancer (PTC) with the BRAFV600E mutation is associated with a poorer prognosis. BRAF inhibitors may demonstrate limited efficacy due to emerging drug resistance. The Warburg effect may have cancer therapeutic implications. It is not known if the BRAFV600E mutation is associated with altered glucose metabolism in PTC.This study examined the effect of the BRAFV600E and DRP1 on various cellular processes in PTC cells, including: cell proliferation, migration, invasion, mitochondrial fission, glucose metabolism, reactive oxygen species (ROS) generation and apoptosis. We used RT-qPCR to assess the expression of key glycolytic enzymes in thyroid cancer tissues. Additionally, the regulatory interaction between BRAFV600E and DRP1 was investigated through Western Blot and immunohistochemical staining. We further evaluated the impact of DRP1 in PTC and inhibitory effects of Dabrafenib and 2-DG in vitro and in vivo.We found that the BRAFV600E mutation significantly augments aerobic glycolysis while suppressing oxidative phosphorylation in PTC. We identified the BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway as a critical mediator in PTC progression. The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway enhances cell proliferation by upregulating HK2 expression and thereby increasing aerobic glycolysis. Secondly, it inhibits apoptosis by promoting mitochondrial fission and reducing ROS levels. Moreover, we demonstrated that the combination therapy of 2-DG and Dabrafenib markedly impedes the progression of BRAFV600E-positive PTC.The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway plays a pivotal role in glucose metabolism reprogramming, contributing to the aggressiveness and progression of BRAFV600E-positive PTC. Our findings suggest that a combined therapeutic approach using 2-DG and Dabrafenib has potential to improve the outcome of PTC patients with BRAFV600E.