Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P. R. China.
Affiliated Stomatology Hospital of Guilin Medical University, Guilin 541004, Guangxi, P. R. China.
Int J Biol Sci. 2022 Jul 27;18(13):4963-4983. doi: 10.7150/ijbs.70007. eCollection 2022.
Pancreatic cancer (PC) is a devastating solid malignancy with a dismal prognosis. The treatment of metastatic PC is a current challenge for medical oncologists due to a lack of early detection, drug resistance, and relapse. Therefore, potential biomarkers and effective therapeutic targets for PC are urgently required. Ceramide-1-phosphate transfer protein (CPTP) is a member of the glycolipid transfer protein family, which is associated with autophagy and inflammation regulation. The roles and mechanisms of in PC have not been clarified. In this study, by RT-qPCR and immunohistochemistry analysis, we found that is highly expressed in PC and is associated with a poor prognosis in PC patients. By using cell counting kit-8, colony formation, transwell and matrigel assays , as well as xenograft model assays , we further proved that enhanced PC cells growth and metastasis. In PC cells, human promotes growth and metastasis via sphingolipid metabolite ceramide and PI4KA/AKT signaling. Sp (specific protein)-1 and Sp3 transcription factors also act as upstream positive regulators of expression in PC cells. Collectively, these findings suggested that may function as a pro-tumorigenic gene in PC cells and could be a promising therapeutic target in PC.
胰腺癌(PC)是一种具有破坏性的实体恶性肿瘤,预后不良。由于缺乏早期检测、耐药性和复发,转移性 PC 的治疗是目前肿瘤内科医生面临的挑战。因此,迫切需要针对 PC 的潜在生物标志物和有效治疗靶点。神经酰胺-1-磷酸转移蛋白(CPTP)是糖脂转移蛋白家族的一员,与自噬和炎症调节有关。在 PC 中作用和机制尚未阐明。在这项研究中,通过 RT-qPCR 和免疫组织化学分析,我们发现 CPTP 在 PC 中高表达,并与 PC 患者的预后不良相关。通过使用细胞计数试剂盒-8、集落形成、Transwell 和 Matrigel 测定以及异种移植模型测定,我们进一步证明 CPTP 增强了 PC 细胞的生长和转移。在 PC 细胞中,CPTP 通过鞘脂代谢物神经酰胺和 PI4KA/AKT 信号促进生长和转移。Sp(特异性蛋白)-1 和 Sp3 转录因子也作为 PC 细胞中 CPTP 表达的上游正调控因子。总之,这些发现表明 CPTP 可能在 PC 细胞中作为一种促肿瘤基因发挥作用,并且可能是 PC 治疗的有希望的靶点。