FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis.
FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis.
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FOXD1通过调节GLUT1介导的有氧糖酵解促进胰腺癌细胞增殖、侵袭和转移
DOI：
10.1038/s41419-022-05213-w
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发表时间：
2022-09-03
影响因子：
9
通讯作者：
Sun, Chengyi
中科院分区：
文献类型：
--
作者：
Cai, Kun;Chen, Shiyu;Zhu, Changhao;Li, Lin;Yu, Chao;He, Zhiwei;Sun, Chengyi
尽管 FOXD1 已被发现参与多种癌症的恶性过程，但其在胰腺癌 (PC) 中的作用尚不清楚。本研究旨在探讨FOXD1在PC中的表达和功能。我们发现，与非肿瘤组织相比，PC 组织中 FOXD1 mRNA 和蛋白表达上调，且 FOXD1 高表达水平与 PC 不良预后指数相关。体外和体内测定结果表明，FOXD1 的过表达可促进有氧糖酵解以及 PC 细胞增殖、侵袭和转移的能力，而 FOXD1 敲低则会抑制这些功能。机制实验结果表明，FOXD1不仅可以直接促进SLC2A1转录，还可以通过RNA诱导的沉默复合物抑制SLC2A1的降解。因此，FOXD1 增强 GLUT1 表达，并最终通过调节有氧糖酵解促进 PC 细胞增殖、侵袭和转移。综上所述，FOXD1 被认为是 PC 的潜在治疗靶点。
Although FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.
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DOI：
10.1038/s41575-021-00457-x
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期刊：
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10.1186/s13046-020-01765-x
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