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LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway

BACKGROUND: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. METHODS: We s...

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Autores principales: Tan, Yuen, Chen, Qingchuan, Pan, Siwei, An, Wen, Xu, Huimian, Xing, Yao, Zhang, Jianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055720/
https://www.ncbi.nlm.nih.gov/pubmed/35488236
http://dx.doi.org/10.1186/s12885-022-09541-0
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author Tan, Yuen
Chen, Qingchuan
Pan, Siwei
An, Wen
Xu, Huimian
Xing, Yao
Zhang, Jianjun
author_facet Tan, Yuen
Chen, Qingchuan
Pan, Siwei
An, Wen
Xu, Huimian
Xing, Yao
Zhang, Jianjun
author_sort Tan, Yuen
collection PubMed
description BACKGROUND: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. METHODS: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. RESULTS: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 10(16)). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. CONCLUSION: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09541-0.
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spelling pubmed-90557202022-05-01 LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway Tan, Yuen Chen, Qingchuan Pan, Siwei An, Wen Xu, Huimian Xing, Yao Zhang, Jianjun BMC Cancer Research BACKGROUND: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. METHODS: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. RESULTS: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 10(16)). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. CONCLUSION: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-022-09541-0. BioMed Central 2022-04-30 /pmc/articles/PMC9055720/ /pubmed/35488236 http://dx.doi.org/10.1186/s12885-022-09541-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Tan, Yuen
Chen, Qingchuan
Pan, Siwei
An, Wen
Xu, Huimian
Xing, Yao
Zhang, Jianjun
LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway
title LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway
title_full LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway
title_fullStr LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway
title_full_unstemmed LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway
title_short LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway
title_sort lmod1, an oncogene associated with lauren classification, regulates the metastasis of gastric cancer cells through the fak-akt/mtor pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9055720/
https://www.ncbi.nlm.nih.gov/pubmed/35488236
http://dx.doi.org/10.1186/s12885-022-09541-0
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