التفاصيل البيبلوغرافية
| العنوان: |
Glutaminase potentiates the glycolysis in esophageal squamous cell carcinoma by interacting with PDK1 |
| المؤلفون: |
Zhu, Guangzhao, Guan, Fangxia, Li, Shenglei, Zhang, Qing, Zhang, Xueying, Qin, Yue, Sun, Zhangzhan, Peng, Shaohua, Cheng, Jiexing, Li, Yiyang, Ren, Ruili, Fan, Tianli, Liu, Hongtao |
| المصدر: |
Molecular Carcinogenesis ; volume 63, issue 5, page 897-911 ; ISSN 0899-1987 1098-2744 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2024 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Increasing evidence has demonstrated that glutaminase (GLS) as a key mitochondrial enzyme plays a pivotal role in glutaminolysis, which widely participates in glutamine metabolism serving as main energy sources and building blocks for tumor growth. However, the roles and molecular mechanisms of GLS in esophageal squamous cell carcinoma (ESCC) remains unknown. Here, we found that GLS was highly expressed in ESCC tissues and cells. GLS inhibitor CB‐839 significantly suppressed cell proliferation, colony formation, migration and invasion of ESCC cells, whereas GLS overexpression displayed the opposite effects. In addition, CB‐839 markedly suppressed glucose consumption and lactate production, coupled with the downregulation of glycolysis‐related proteins HK2, PFKM, PKM2 and LDHA, whereas GLS overexpression exhibited the adverse results. In vivo animal experiment revealed that CB‐839 dramatically suppressed tumor growth, whereas GLS overexpression promoted tumor growth in ESCC cells xenografted nude mice. Mechanistically, GLS was localized in mitochondria of ESCC cells, which interacted with PDK1 protein. CB‐839 attenuated the interaction of GLS and PDK1 in ESCC cells by suppressing PDK1 expression, which further evoked the downregulation of p‐PDHA1 (s293), however, GLS overexpression markedly enhanced the level of p‐PDHA1 (s293). These findings suggest that interaction of GLS with PDK1 accelerates the glycolysis of ESCC cells by inactivating PDH enzyme, and thus targeting GLS may be a novel therapeutic approach for ESCC patients. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/mc.23696 |
| الإتاحة: |
https://doi.org/10.1002/mc.23696Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.5A1A96C7 |
| قاعدة البيانات: |
BASE |
