PLAGL2‐EGFR‐HIF‐1/2α Signaling Loop Promotes HCC Progression and Erlotinib Insensitivity
| العنوان: | PLAGL2‐EGFR‐HIF‐1/2α Signaling Loop Promotes HCC Progression and Erlotinib Insensitivity |
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| المؤلفون: | Beiying Dai, Hongbao Yang, Jifeng Feng, Yaohong Shi, Decai Yu, Lanxin Li, Jiaping Ni, Duowei Wang, Guilai Liu, Amir Hossain, Mo Wu, Weiwei Hu, Lutz Birnbaumer, Yong Yang, Hanrui Bian, Yumeng Shen, Shufang Zheng, Haixin Guo, Zhoutong Tian, Qin Zhang, Jun Yu |
| المصدر: | Hepatology. 73:674-691 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Kaplan-Meier Estimate, medicine.disease_cause, Mice, 0302 clinical medicine, Cell Movement, Basic Helix-Loop-Helix Transcription Factors, RNA-Seq, Epidermal growth factor receptor, Feedback, Physiological, Regulation of gene expression, Gene knockdown, Liver Neoplasms, RNA-Binding Proteins, Middle Aged, Cell cycle, Up-Regulation, DNA-Binding Proteins, ErbB Receptors, Gene Expression Regulation, Neoplastic, Liver, Gene Knockdown Techniques, Disease Progression, Female, 030211 gastroenterology & hepatology, Erlotinib, Signal Transduction, medicine.drug, Adult, Carcinoma, Hepatocellular, Biology, Erlotinib Hydrochloride, 03 medical and health sciences, Cyclin D1, Cell Line, Tumor, medicine, Animals, Humans, Neoplasm Invasiveness, neoplasms, Aged, Cell Proliferation, Hepatology, Tumor hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Xenograft Model Antitumor Assays, digestive system diseases, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, biology.protein, Tumor Hypoxia, Carcinogenesis, Transcription Factors |
| الوصف: | Background and aims Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, hence a major public health threat. Pleomorphic adenoma gene like-2 (PLAGL2) has been reported to play a role in tumorigenesis. However, its precise function in HCC remains poorly understood. Approach and results In this study, we demonstrated that PLAGL2 was up-regulated in HCC compared with that of adjacent nontumorous tissues and also correlated with overall survival times. We further showed that PLAGL2 promoted HCC cell proliferation, migration, and invasion both in vitro and in vivo. PLAGL2 expression was positively correlated with epidermal growth factor receptor (EGFR) expression. Mechanistically, this study demonstrated that PLAGL2 functions as a transcriptional regulator of EGFR and promotes HCC cell proliferation, migration, and invasion through the EGFR-AKT pathway. Moreover, hypoxia was found to significantly induce high expression of PLAGL2, which promoted hypoxia inducible factor 1/2 alpha subunit (HIF1/2A) expression through EGFR. Therefore, this study demonstrated that a PLAGL2-EGFR-HIF1/2A signaling loop promotes HCC progression. More importantly, PLAGL2 expression reduced hepatoma cells' response to the anti-EGFR drug erlotinib. PLAGL2 knockdown enhanced the response to erlotinib. Conclusions This study reveals the pivotal role of PLAGL2 in HCC cell proliferation, metastasis, and erlotinib insensitivity. This suggests that PLAGL2 can be a potential therapeutic target of HCC. |
| تدمد: | 1527-3350 0270-9139 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::04e65319cfb6d147519c7aef731bd183Test https://doi.org/10.1002/hep.31293Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....04e65319cfb6d147519c7aef731bd183 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15273350 02709139 |
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