Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China.
Exp Cell Res. 2018 Sep 1;370(1):46-57. doi: 10.1016/j.yexcr.2018.06.007. Epub 2018 Jun 15.
The tumor starvation microenvironment plays a pivotal role in the malignant progression of cancer, which is closely related to autophagy, glycolysis, and epithelial mesenchymal transition (EMT). Nevertheless, the underlying mechanisms of the starvation-mediated malignant phenotype are still not well documented. In this study, we aimed to investigate the effect of starvation on glycolysis, autophagy, and EMT in OSCC and to further elucidate the key metabolic modulator. The results showed that starvation can induce autophagy, EMT, and enhanced glycolysis in OSCC cells. We determined that the expression of the key glycolytic enzyme phosphofructokinase-platelet (PFKP) obviously increased under starvation conditions and that PFKP knockdown inhibited starvation-mediated glycolysis, autophagy and EMT in OSCC cells. Moreover, we confirmed that PFKP knockdown inhibited OSCC xenograft growth in vivo. In addition, PFKP expression was significantly increased in OSCC patients and its upregulation was associated with the presence of tumor pathological differentiation and lymph node metastasis. Taken together, our findings demonstrate that PFKP is necessary for starvation-mediated autophagy, glycolysis, and EMT, thereby promoting the malignant progression of OSCC.
肿瘤饥饿微环境在癌症的恶性进展中起着关键作用，与自噬、糖酵解和上皮间质转化（EMT）密切相关。然而，饥饿介导的恶性表型的潜在机制仍未得到很好的记录。在这项研究中，我们旨在研究饥饿对 OSCC 中糖酵解、自噬和 EMT 的影响，并进一步阐明关键的代谢调节剂。结果表明，饥饿可诱导 OSCC 细胞发生自噬、EMT 和增强的糖酵解。我们确定在饥饿条件下关键糖酵解酶磷酸果糖激酶血小板（PFKP）的表达明显增加，并且 PFKP 敲低抑制 OSCC 细胞中饥饿介导的糖酵解、自噬和 EMT。此外，我们证实 PFKP 敲低抑制了 OSCC 异种移植在体内的生长。此外，PFKP 在 OSCC 患者中的表达明显增加，其上调与肿瘤病理分化和淋巴结转移的存在相关。总之，我们的研究结果表明，PFKP 是饥饿介导的自噬、糖酵解和 EMT 所必需的，从而促进了 OSCC 的恶性进展。
