NDLI: 4.1B suppresses cancer cell proliferation by binding to EGFR P13 region of intracellular juxtamembrane segment

Content Provider	Springer Nature : BioMed Central
Author	Xue, Fumin An, Chao Chen, Lixiang Liu, Gang Ren, Feifei Guo, Xinhua Sun, Haibin Mei, Lu Sun, Xiangdong Li, Jinpeng Tang, Youcai An, Xiuli Zheng, Pengyuan
Abstract	Background Gastric cancer (GC) has high incidence and mortality worldwide. However, the underlying mechanisms that regulate gastric carcinogenesis are largely undefined. 4.1B is an adaptor protein found at the interface of membrane and the cytoskeleton. Previous studies demonstrated that 4.1B serves as tumor suppressor. Results We showed that 4.1B expression was decreased or lost in most GC patients. The expression pattern of it was tightly correlated with tumor size, TNM stage and overall survival (OS). We further showed that 4.1B inhibited the proliferation of two GC cell lines, MGC-803 and MKN-45, by impeding the EGFR/MAPK/ERK1/2 and PI3K/AKT pathways. A similar phenotype was also observed in immortalized mouse embryonic fibroblasts (MEF) derived from wild type (WT) and 4.1B knock-out (BKO) mice. Additionally, immunofluorescence (IF) staining and Co-IP showed that protein 4.1B bound to EGFR. Furthermore, the FERM domain of 4.1B interacted with EGFR through the initial 13 amino acids (P13) of the intracellular juxtamembrane (JM) segment of EGFR. The binding of 4.1B to EGFR inhibited dimerization and autophosphorylation of EGFR. Conclusion Our present work revealed that 4.1B plays important regulatory roles in the proliferation of GC cells by binding to EGFR and inhibiting EGFR function through an EGFR/MAPK/ERK1/2 pathway. Our results provide novel insight into the mechanism of the development and progression of GC.
Related Links	https://biosignaling.biomedcentral.com/counter/pdf/10.1186/s12964-019-0431-6.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12964-019-0431-6
Journal	Cell Communication and Signaling
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2019-09-06
Access Restriction	Open
Subject Keyword	Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Gastric cancer Protein 4.1B EGFR Sp1 Tumor suppressor
Content Type	Text
Resource Type	Article
Subject	Biochemistry Cell Biology Molecular Biology
Journal Impact Factor	8.2/2023
5-Year Journal Impact Factor	8/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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