journal article·2024-04Open access

Myofibrillogenesis Regulator‐1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin‐Protein Ligase Itchy Homolog in the Metastasis of Non‐Small Cell Lung Cancer

Wenxia Zhao, Yang Li, Hanzeng Cheng, Mengyan Wang, Zhishuo Zhang, Meilian Cai, Cong Zhao, Xiaoming Xi, Xiaojun Zhao, Wuli Zhao, Yajun Yang, Rongguang Shao

Advanced Science· Volume 11· Issue 15

Abstract

Abstract Myofibrillogenesis regulator‐1 (MR‐1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR‐1 on the development and metastasis of non‐small cell lung cancer (NSCLC). MR‐1 is upregulated in NSCLC and positively associated with poor prognosis. The overexpression of MR‐1 promotes the metastasis of NSCLC cells by stabilizing the expression of Notch3‐ICD (NICD3) in the cytoplasm through enrichment analysis, in vitro and in vivo experimental researches. And Notch3 signaling can upregulate many genes related to metastasis. The stabilizing effect of MR‐1 on NICD3 is achieved through the mono‐ubiquitin lysosomal pathway and the specific E3 ubiquitin ligase is Itchy homolog (ITCH). There is a certain interaction between MR‐1 and NICD3. Elevated MR‐1 can affect the level of ITCH phosphorylation, reduce its E3 enzyme activity, and thus lead to reduce the ubiquitination and degradation of NICD3. Interference with the interaction between MR‐1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR‐1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Ubiquitin and proteasome pathways · Microtubule and mitosis dynamics · Cancer, Hypoxia, and Metabolism

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

NHC Key Laboratory of Antibiotic Bioengineering, Laboratory of Oncology Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 Beijing P. R. China

Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences Beijing 100050 P. R. China

Zhujiang Hospital Southern Medical University Guangzhou Guangdong 510280 P. R. China

Department of Emergency Xinhua Hospital Shanghai Jiaotong University School of Medicine Shanghai 200092 P. R. China

Department of Organ Transplantation and Hepatobiliary Surgery The First Hospital of China Medical University Shenyang Liaoning 110001 P. R. China

State Key Laboratory of Respiratory Health and Multimorbidity Ministry of Health Laboratory of Oncology Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China

Funding

National Natural Science Foundation of China · Chinese Academy of Medical Sciences Initiative for Innovative Medicine · National Key Research and Development Program of China

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