LIMD1 is a Survival Prognostic Marker of Gastric Cancer and Hinders Tumor Progression by Suppressing Activation of YAP1

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2018 Oct 24

PMID 30349368

Citations 8

Authors

Di Zhang

Song Li

Wenbin Yu

Cheng Chen

Teng Liu

Yiting Sun

Zeyi Zhao

Lian Liu

Affiliations

Soon will be listed here.

Abstract

Purpose: The purpose of this study was to investigate the clinical significance of LIMD1 and its biological roles in gastric cancer (GC).

Materials And Methods: The prognostic value of LIMD1 in GC patients was determined by the online tool Kaplan-Meier Plotter. The biological functions of LIMD1 in GC were examined by in vitro assays, including proliferation, anchorage-independent growth, migration, invasion, and epithelial to mesenchymal transition (EMT) assays. The levels of downstream YAP1 regulated by LIMD1 were measured by Western blot analysis, and the sub-localization of YAP1 in GC cells was visualized by immunofluorescence staining. Differential expression levels and copy number levels of LIMD1 between GC and normal tissues were compared using the Oncomine database. A correlation of LIMD1 mRNA level and the copy number level was depicted by cBioPortal. We also evaluated the methylation status around the LIMD1 genes by Wanderer.

Results: The expression level of LIMD1 positively correlated with the prognosis of GC patients regardless of tumor stage, size, lymph node, metastasis, Lauren's classification, differentiation, gender, treatment, and amplification status. Overexpression of LIMD1 impeded the tumor growth, cell motility, invasiveness, and metastasis, and knockdown of LIMD1 promoted these phenotypes in GC cells. Mechanistically, YAP1 was one of the downstream effectors of LIMD1; LIMD1 suppressed the expression of YAP1 as well as its intracellular translocation. Furthermore, we found that LIMD1 expression was reduced in some of the GC profiling datasets. Gene deletion, instead of DNA methylation, contributed to the reduced expression of LIMD1 in GC.

Conclusion: Our results identified LIMD1 as a convincing prognostic marker as well as a potentially therapeutic target for GC.

Citing Articles

Upregulated LIMD1 alleviates pressure overload-induced cardiac hypertrophy via inhibits YAP1/AKT/GSK3β signaling.

Xie F, Yuan B, Zhang Y, Chen L, Zhong Y, Xu Q PLoS One. 2025; 20(2):e0316149.

PMID: 39937832 PMC: 11819601. DOI: 10.1371/journal.pone.0316149.

PLOD3 regulates the expression of YAP1 to affect the progression of non-small cell lung cancer via the PKCδ/CDK1/LIMD1 signaling pathway.

Li W, Huang K, Wen F, Cui G, Guo H, Zhao S Lab Invest. 2022; 102(4):440-451.

PMID: 35039611 DOI: 10.1038/s41374-021-00674-7.

New Look of EBV LMP1 Signaling Landscape.

Wang L, Ning S Cancers (Basel). 2021; 13(21).

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Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes.

Davidson K, Grevitt P, Contreras-Gerenas M, Bridge K, Hermida M, Shah K Cell Death Dis. 2021; 12(11):1075.

PMID: 34764236 PMC: 8586256. DOI: 10.1038/s41419-021-04355-7.

Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma.

Wang L, Sparks-Wallace A, Casteel J, Howell M, Ning S Front Oncol. 2021; 11:632638.

PMID: 33869018 PMC: 8044451. DOI: 10.3389/fonc.2021.632638.

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