Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC10506284 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Jiang Yingming Y Feng Yanchun Y Huang Jintuan J Huang Zhenze Z Tan Rongchang R Li Tuoyang T Chen Zijian Z Tang Xiaocheng X Qiu Jun J Li Chujun C Chen Hao H Yang Zuli Z

Journal of translational medicine 20230917 1

<h4>Background</h4>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).<h4>Methods</h4>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 rev ...[more]

PMID: 37718450

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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