LACTB promotes metastasis of nasopharyngeal carcinoma via activation of ERBB3/EGFR-ERK signaling resulting in unfavorable patient survival
| Autor: | Zhi-Jie Liu, Di-Tian Shu, Li-Xia Peng, Ling-Ling Guo, Li-Sheng Zheng, De-Huan Xie, Dong-Fang Meng, Chang-Zhi Li, Xing-Si Peng, Rui Sun, Liang Xu, Jun-Ping Yang, Ming-Dian Wang, Fei-Fei Luo, Bi-Jun Huang, Ping Xie, Yan-Hong Lang, Chao-Nan Qian, Si-Ting Lin, Yan Mei, Yuan-Yuan Qiang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Receptor ErbB-3 MAP Kinase Signaling System Motility Mice Nude Biology beta-Lactamases Metastasis Mitochondrial Proteins 03 medical and health sciences Histone H3 Mice 0302 clinical medicine Cell Movement Cell Line Tumor otorhinolaryngologic diseases medicine Animals Humans ERBB3 Neoplasm Metastasis Histone H3 acetylation Promoter Regions Genetic Cell Proliferation Nasopharyngeal Carcinoma Membrane Proteins Nasopharyngeal Neoplasms medicine.disease Epithelium Gene expression profiling ErbB Receptors stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Oncology Nasopharyngeal carcinoma 030220 oncology & carcinogenesis Cancer research Female Signal Transduction |
| Zdroj: | Cancer letters. 498 |
| ISSN: | 1872-7980 |
| Popis: | Nasopharyngeal carcinoma (NPC) originates in the nasopharyngeal epithelium and has the highest metastatic rate among head and neck cancers. Distant metastasis is the main reason for treatment failure with the underlying mechanisms remaining unclear. By comparing the expression profiling of NPCs versus non-cancerous nasopharyngeal tissues, we found LACTB was highly expressed in the tumor tissues. We found that elevated expression of the LACTB protein in primary NPCs correlated with poorer patient survival. LACTB is known to be a serine protease and a ubiquitous mitochondrial protein localized in the intermembrane space. Its role in tumor biology remains controversial. We found that the different methylation pattern of LACTB promoter led to its differential expression in NPC cells. Overexpressing LACTB in NPC cells promoted their motility in vitro and metastasis in vivo. While knocking down LACTB reduced the metastasis capability of NPC cells. However, LACTB did not influence cellular proliferation. We further found the role of LACTB in promoting NPC metastasis depended on the activation of ERBB3/EGFR-ERK signaling, which in turn, affected the stability and the following acetylation of histone H3. These findings may shed light on unveiling the mechanisms of NPC metastasis. |
| Databáze: | OpenAIRE |
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