2. Academic Validation
  3. Down-regulation of MFNG promotes the metastatic potential of lung adenocarcinoma by regulating TGF-β/Smad signaling

Down-regulation of MFNG promotes the metastatic potential of lung adenocarcinoma by regulating TGF-β/Smad signaling

  • iScience. 2025 Sep 24;28(11):113647. doi: 10.1016/j.isci.2025.113647.
Tianshu Miao 1,  Yilin Zhang 1,  Feng Tian 2,  Xiaoying Xu 2,  Qin Wei 1,  Xiaoyu Jiang 1,  Lijuan Ma 1,  Pengju Zhang 1,  Fengzhe Chen 3,  Xiaoyan Lin 2
Affiliations

Affiliations

  • 1 Key Laboratory Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 2 Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
  • 3 Department of Infectious Disease, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250013, China.
PMID: 41210989 DOI: 10.1016/j.isci.2025.113647
Abstract

Manic Fringe (MFNG), a fucose-specific β-1,3-N-acetylglucosaminyltransferase, is critically involved in different cancers. However, the potential role and underlying mechanism of MFNG in the progression of lung adenocarcinoma (LUAD) remain unclear. Here, we found that MFNG was significantly down-regulated in LUAD tissues compared with adjacent non-cancerous tissues. Moreover, its decreased expression was associated with aggressive LUAD characteristics, including high grade and poor prognosis. Functional studies revealed that MFNG deficiency promoted migratory and invasive capabilities as well as the epithelial-mesenchymal transition of LUAD cells in vitro and metastatic potential in vivo. Mechanistically, we found that MFNG silencing resulted in a remarkable activation of the TGF-β/Smad signaling pathway. Pharmacological treatment with a TGF-β Receptor kinase inhibitor alleviated the progressive phenotypes of LUAD cells induced by MFNG loss. Together, our results reveal a potential mechanism by which MFNG regulates LUAD progression and suggest that patients with advanced LUAD exhibiting MFNG deficiency may benefit from TGF-β signaling inhibition.

Keywords

Biological sciences; Cancer; Glycobiology.

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