2. Academic Validation
  3. IL6/STAT3 induced GRWD1 mediates aerobic glycolysis via P53/GLUT1 signal axis in colon carcinoma

IL6/STAT3 induced GRWD1 mediates aerobic glycolysis via P53/GLUT1 signal axis in colon carcinoma

  • Sci Rep. 2025 Sep 29;15(1):33534. doi: 10.1038/s41598-025-18114-7.
Jin Shang 1,  Hong-Yue Ren 2,  Fa-Hui Liu 3,  Dong-Hua Liu 3,  Shi-Hang Tang 3,  Guo-Xian Guan 4,  Guo-Qiang Su 5,  Dong-Yan Shen 6,  Xin Zhou 7
Affiliations

Affiliations

  • 1 Cancer Research Center, School of Medicine, Xiamen University, 4221 Xiang'an South Road, Xiamen, 361102, Fujian Province, China.
  • 2 Basic Medical College, Zhangzhou Health Vocational College, Zhangzhou, 363000, Fujian Province, China.
  • 3 Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University School of Medicine, School of Medicine, Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, Fujian Province, China.
  • 4 Department of Colorectal Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, People's Republic of China.
  • 5 Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, Fujian Province, China. suguoqiang@xmu.edu.cn.
  • 6 Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University School of Medicine, School of Medicine, Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, Fujian Province, China. shendongyan@163.com.
  • 7 Department of Colorectal Tumor Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, Fujian Province, China. 1012256893@qq.com.
PMID: 41022893 DOI: 10.1038/s41598-025-18114-7
Abstract

GRWD1, a novel WD40-repeat-containing protein designated glutamate-rich WD repeat, is highly expressed in CRC and participates in a series of oncogenic activities. However, the cause of GRWD1 overexpression and its oncogenic mechanism in CRC remains elusive. This study revealed that GRWD1 was correlated with inflammation and was progressively upregulated during the progression of Azoxymethane/Dextran sodium sulfate (AOM/DSS) in a mouse model. Moreover, GRWD1 was activated by the IL-6/STAT3 signal pathway in CRC cells. Besides, it promoted the degradation of p53 and further induced GLUT1 to facilitate aerobic glycolysis in CRC. Taken together, GRWD1 played an oncogenic role in tumorigenesis of CRC and represented a promising therapeutic target.

Keywords

Aerobic glycolysis; Colon carcinoma; GLUT1; GRWD1; IL-6/STAT3.

Figures
Products