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Cellular Oncology

Cellular Oncology

IF: 4.8
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RAB37 suppresses the EMT, migration and invasion of gastric cancer cells by mediating autophagic degradation of β-catenin

Published:1 December 2024 DOI: 10.1007/s13402-024-01028-3 PMID: 39699800
Jiangling Duan,?Xiuyin Guan,?Jiaxin Xue,?Jiayu Wang,?Zhiwei Wang,?Xuan Chen,?Wen Jiang,?Wannian Sui,?Yongfang Song,?Tianshu Li,?Dewang Rao,?Xueyan Wu,?Ming Lu

Abstract

Background: Gastric cancer, characterized by its high morbidity and mortality rates, exhibits low levels of RAB37. The role and molecular mechanisms of RAB37, a small GTPase, in the pathogenesis of gastric cancer are still unclear.

Methods: We assessed RAB37 expression in gastric cancer cells using quantitative Polymerase Chain Reaction (qPCR), Western blot, and immunohistochemical staining (IHC), and analyzed EMT marker proteins and autophagy changes via Western blot, immunofluorescence (IF), and transmission electron microscopy (TEM). Co-immunoprecipitation (co-IP) was used to identify protein-protein interactions. We studied the migration and invasion of gastric cancer cells using wound healing and transwell assays in vitro and a mouse pulmonary metastasis model in vivo.

Results: Overexpression of RAB37 suppressed EMT, invasion, and migration while enhancing autophagy in gastric cancer cells, which was dependent on its GTPase activity. However, all these effects could be reversed by the autophagy inhibitor chloroquine. Regarding the molecular mechanism, RAB37 strengthened the interaction between p62 and β-catenin, which consequently enhanced the p62-mediated autophagic degradation of β-catenin. Furthermore, RAB37 curbed the pulmonary metastasis of both general and cisplatin-resistant gastric cancer cells.

Conclusion: The low level of RAB37 reduces interaction between p62 and β-catenin and then the autophagic degradation of β-catenin, thereby promoting the EMT, invasion, and migration in gastric cancer cells. The low expression of RAB37 in gastric cancer suggests a potential therapeutic target, especially for cisplatin-resistant gastric cancer.

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MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$3568.00
MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$3568.00
MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$3568.00
MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$3568.00
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3-METHYLADENINE 5142-23-4 C6H7N5 392 suppliers $12.00-$1890.00
3-METHYLADENINE 5142-23-4 C6H7N5 392 suppliers $12.00-$1890.00
BAFILOMYCIN A1 88899-55-2 C35H58O9 304 suppliers $80.00-$2180.00
BAFILOMYCIN A1 88899-55-2 C35H58O9 304 suppliers $80.00-$2180.00

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