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LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer

BACKGROUND: Ladinin-1 (LAD1), an anchoring filament protein, has been associated with several cancer types, including cancers of the colon, lungs, and breast. However, it is still unclear how and why LAD1 causes gastric cancer (GC). METHODS: Multiple in vitro and in vivo, functional gains and loss e...

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Autores principales: Jiang, Yingming, Feng, Yanchun, Huang, Jintuan, Huang, Zhenze, Tan, Rongchang, Li, Tuoyang, Chen, Zijian, Tang, Xiaocheng, Qiu, Jun, Li, Chujun, Chen, Hao, Yang, Zuli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506284/
https://www.ncbi.nlm.nih.gov/pubmed/37718450
http://dx.doi.org/10.1186/s12967-023-04401-2
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author Jiang, Yingming
Feng, Yanchun
Huang, Jintuan
Huang, Zhenze
Tan, Rongchang
Li, Tuoyang
Chen, Zijian
Tang, Xiaocheng
Qiu, Jun
Li, Chujun
Chen, Hao
Yang, Zuli
author_facet Jiang, Yingming
Feng, Yanchun
Huang, Jintuan
Huang, Zhenze
Tan, Rongchang
Li, Tuoyang
Chen, Zijian
Tang, Xiaocheng
Qiu, Jun
Li, Chujun
Chen, Hao
Yang, Zuli
author_sort Jiang, Yingming
collection PubMed
description BACKGROUND: Ladinin-1 (LAD1), an anchoring filament protein, has been associated with several cancer types, including cancers of the colon, lungs, and breast. However, it is still unclear how and why LAD1 causes gastric cancer (GC). METHODS: Multiple in vitro and in vivo, functional gains and loss experiments were carried out in the current study to confirm the function of LAD1. Mass spectrometry was used to find the proteins that interact with LAD1. Immunoprecipitation analyses revealed the mechanism of LAD1 involved in promoting aggressiveness. RESULTS: The results revealed that the LAD1 was overexpressed in GC tissues, and participants with increased LAD1 expression exhibited poorer disease-free survival (DFS) and overall survival (OS). Functionally, LAD1 promotes cellular invasion, migration, proliferation, and chemoresistance in vivo and in vitro in the subcutaneous patient-and cell-derived xenograft (PDX and CDX) tumor models. Mechanistically, LAD1 competitively bound to Vimentin, preventing it from interacting with the E3 ubiquitin ligase macrophage erythroblast attacher (MAEA), which led to a reduction in K48-linked ubiquitination of Vimentin and an increase in Vimentin protein levels in GC cells. CONCLUSIONS: In conclusion, the current investigation indicated that LAD1 has been predicted as a possible prognostic biomarker and therapeutic target for GC due to its ability to suppress Vimentin–MAEA interaction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04401-2.
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spelling pubmed-105062842023-09-19 LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer Jiang, Yingming Feng, Yanchun Huang, Jintuan Huang, Zhenze Tan, Rongchang Li, Tuoyang Chen, Zijian Tang, Xiaocheng Qiu, Jun Li, Chujun Chen, Hao Yang, Zuli J Transl Med Research BACKGROUND: Ladinin-1 (LAD1), an anchoring filament protein, has been associated with several cancer types, including cancers of the colon, lungs, and breast. However, it is still unclear how and why LAD1 causes gastric cancer (GC). METHODS: Multiple in vitro and in vivo, functional gains and loss experiments were carried out in the current study to confirm the function of LAD1. Mass spectrometry was used to find the proteins that interact with LAD1. Immunoprecipitation analyses revealed the mechanism of LAD1 involved in promoting aggressiveness. RESULTS: The results revealed that the LAD1 was overexpressed in GC tissues, and participants with increased LAD1 expression exhibited poorer disease-free survival (DFS) and overall survival (OS). Functionally, LAD1 promotes cellular invasion, migration, proliferation, and chemoresistance in vivo and in vitro in the subcutaneous patient-and cell-derived xenograft (PDX and CDX) tumor models. Mechanistically, LAD1 competitively bound to Vimentin, preventing it from interacting with the E3 ubiquitin ligase macrophage erythroblast attacher (MAEA), which led to a reduction in K48-linked ubiquitination of Vimentin and an increase in Vimentin protein levels in GC cells. CONCLUSIONS: In conclusion, the current investigation indicated that LAD1 has been predicted as a possible prognostic biomarker and therapeutic target for GC due to its ability to suppress Vimentin–MAEA interaction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04401-2. BioMed Central 2023-09-17 /pmc/articles/PMC10506284/ /pubmed/37718450 http://dx.doi.org/10.1186/s12967-023-04401-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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, visit http://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
Jiang, Yingming
Feng, Yanchun
Huang, Jintuan
Huang, Zhenze
Tan, Rongchang
Li, Tuoyang
Chen, Zijian
Tang, Xiaocheng
Qiu, Jun
Li, Chujun
Chen, Hao
Yang, Zuli
LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer
title LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer
title_full LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer
title_fullStr LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer
title_full_unstemmed LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer
title_short LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer
title_sort lad1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506284/
https://www.ncbi.nlm.nih.gov/pubmed/37718450
http://dx.doi.org/10.1186/s12967-023-04401-2
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