2. Academic Validation
  3. 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

  • Cell Death Dis. 2022 Sep 3;13(9):765. doi: 10.1038/s41419-022-05213-w.
Kun Cai  # 1 2 3 4,  Shiyu Chen  # 1 3 4 5,  Changhao Zhu  # 6,  Lin Li 1 3 4 5,  Chao Yu 1 2 3 4,  Zhiwei He 7 8,  Chengyi Sun 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, China.
  • 2 College of Clinical Medicine, Guizhou Medical University, Guiyang, 550001, China.
  • 3 Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, 550001, China.
  • 4 Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University, 550001, Guiyang, China.
  • 5 College of Basic Medicine, Guizhou Medical University, 550001, Guiyang, China.
  • 6 Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550001, China.
  • 7 Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Shenzhen University General Hospital, Shenzhen, 518000, China.
  • 8 Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, 518000, China.
  • 9 Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, China. sunchengyi2014@163.com.
  • 10 College of Clinical Medicine, Guizhou Medical University, Guiyang, 550001, China. sunchengyi2014@163.com.
  • 11 Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, 550001, China. sunchengyi2014@163.com.
  • 12 Key Laboratory of Liver, Gallbladder, Pancreas and Spleen of Guizhou Medical University, 550001, Guiyang, China. sunchengyi2014@163.com.
  • # Contributed equally.
PMID: 36057597 DOI: 10.1038/s41419-022-05213-w
Abstract

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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