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Suppressing the MLK3 promotes glutamine metabolism: mechanism and implications in progression of colon cancer

  • Ziqi Sui1,2
  • Kejia Wu3
  • Ruiping Shi4
  • Shuqiu Wang1,*,

1Key Laboratory of Microecology-immune Regulatory Network and Related Diseases, School of Basic Medicine, Jiamusi University, 154000 Jiamusi, Heilongjiang, China

2Department of Gastroenterology, The First People’s Hospital of LinPing District, 310000 Hangzhou, Zhejiang, China

3Department of Endocrinology, First Affiliated Hospital of Jiamusi University, 154000 Jiamusi, Heilongjiang, China

4First Affiliated Hospital of Jiamusi University, 154000 Jiamusi, Heilongjiang, China

DOI: 10.22514/jomh.2023.045 Vol.19,Issue 6,June 2023 pp.26-33

Submitted: 16 April 2023 Accepted: 10 May 2023

Published: 30 June 2023

*Corresponding Author(s): Shuqiu Wang E-mail:


This study was designed to explore the potential role of mixed-lineage protein kinase 3 (MLK3) in colorectal cancer (CRC) progression and its relationship with glutamine metabolism. The immunohistochemical staining results of MLK3 were primarily collected through 100 CRC patients. Wound healing and transwell assays were used to detect migration ability of CRC cells by transfecting cells with siMlk3. Gene set variation analysis (GSVA) and Spearman’s rank correlation coefficient were used as bioinformatics tools to explore the signaling pathways related to MLK3. Western blotting was performed to analyze the downstream of glutamine metabolism. The results suggested an increased expression of MLK3 in CRC tissues, which was related to adverse clinicopathological characteristics in those CRC patients. Knockdown of MLK3 inhibited the proliferative and migratory potential of CRCs. Bioinformatics analysis confirmed the relationship between MLK3 expression and cancer malignancy related signaling pathways. CRC cell lines transfected with siMlk3 suppressed glutamine metabolism by downregulating the glutamine transporter alanine-serine-cysteine transporter 2 (ASCT2). These results suggested the vital role of MLK3 in CRC progression, which may be related to the suppression of glutamine transporter, namely alanine, serine, cysteine transporter 2 (ASCT2).


Colorectal cancer; MLK3; Glutamine metabolism; ASCT2

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Ziqi Sui,Kejia Wu,Ruiping Shi,Shuqiu Wang. Suppressing the MLK3 promotes glutamine metabolism: mechanism and implications in progression of colon cancer. Journal of Men's Health. 2023. 19(6);26-33.


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