Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer

Li, Jin, Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Shi, Xiaoshun, Chen, Jingyi, Feng, Fenglan, Chen, Yaoqi, Xiao, Yiren, Shen, Jianfei, Li, Peng, Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 and He, Jianxing 2016. Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer. Oncotarget 7 , pp. 15678-15689. 10.18632/oncotarget.7463

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Abstract

Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Impact Journals
ISSN:	1949-2553
Funders:	Cardiff China Medical Scholarship
Date of First Compliant Deposit:	8 April 2016
Date of Acceptance:	26 January 2016
Last Modified:	05 May 2023 22:06
URI:	https://orca.cardiff.ac.uk/id/eprint/88954

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