Although cilia loss and cell transformation are frequently observed in the early stage of tumorigenesis, the roles of cilia in cell transformation are unknown. In this study, disrupted ciliogenesis was observed in cancer cells and pancreatic cancer tissues, which facilitated oncogene-induced transformation of normal pancreatic cells (HPDE6C7) and NIH3T3 cells through activating the mevalonate (MVA) pathway. Disruption of ciliogenesis up-regulated MVA enzymes through β catenin–T cell factor (TCF) signaling, which synchronized with sterol regulatory element binding transcription factor 2 (SREBP2), and the regulation of MVA by β-catenin–TCF signaling was recapitulated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) and human PDAC samples. Moreover, disruption of ciliogenesis by depleting Tg737 dramatically promoted tumorigenesis in the PDAC mouse model, driven by Kras^G12D, which was inhibited by statin, an inhibitor of the MVA pathway. Collectively, this study emphasizes the crucial roles of cilia in governing the early steps of the transformation by activating the MVA pathway, suggesting that statin has therapeutic potential for pancreatic cancer treatment.

尽管在肿瘤发生的早期经常观察到纤毛损失和细胞转化，但是纤毛在细胞转化中的作用尚不清楚。在这项研究中，在癌细胞和胰腺癌组织中观察到纤溶发生，通过激活甲羟戊酸（MVA）途径促进癌基因诱导的正常胰腺细胞（HPDE6C7）和NIH3T3细胞转化。通过β连环蛋白-T细胞因子（TCF）信号转导纤溶作用而上调MVA酶，该信号与固醇调节元件结合转录因子2（SREBP2）同步，并且在β-连环蛋白-TCF信号转导中对MVA的调节进行了概括。胰腺导管腺癌（PDAC）和人PDAC样品的小鼠模型。此外，通过消耗ciliogenesis的破坏Tg737在Kras ^G12D的驱动下，PDAC小鼠模型极大地促进了PDAC小鼠的肿瘤发生，而他汀类药物则抑制了MVA途径。总体而言，这项研究强调纤毛在通过激活MVA途径来控制转化的早期步骤中的关键作用，表明他汀类药物具有治疗胰腺癌的潜力。