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

Oncotarget
Jin LiJianxing He

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.

References

Feb 7, 2002·The European Respiratory Journal·E BrambillaY Shimosato
Dec 23, 2003·Cellular Signalling·Anja NoheNils O Petersen
Jan 22, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christian ParrWen G Jiang
Feb 27, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tarek A SamadClifford J Woolf
Jan 27, 2005·The Journal of Biological Chemistry·Tarek A SamadClifford J Woolf
Mar 29, 2007·The Journal of Biological Chemistry·Sabine ConradThomas Skutella
Sep 27, 2007·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E-L AlarmoA Kallioniemi
Aug 16, 2008·Journal of Neurochemistry·Gregor SchaffarBernhard K Mueller
Nov 5, 2008·Cancer Letters·Emma-Leena AlarmoAnne Kallioniemi
Dec 17, 2008·Cell Research·Yao-Yun LiangXia Lin
Mar 28, 2009·Biochemical and Biophysical Research Communications·Xiaoxiang LiuToshihide Yamashita
Oct 3, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Hongjiang SongChunfang Song
Oct 20, 2009·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Kohei Miyazono
Feb 25, 2010·Annals of Surgical Oncology·Stephen B Edge, Carolyn C Compton
Apr 24, 2010·Journal of Oncology·Raka BhattacharyaRhoda M Alani
Oct 16, 2010·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Wen G JiangKeith G Harding
Jan 5, 2011·Frontiers in Bioscience (Landmark Edition)·Lin YeWen G Jiang
Jun 5, 2012·The New England Journal of Medicine·Suzanne L TopalianMario Sznol
Oct 12, 2012·Journal of the National Comprehensive Cancer Network : JNCCN·David S EttingerUNKNOWN NCCN (National Comprehensive Cancer Network)
Apr 23, 2014·The Journal of Experimental Medicine·Yanping XiaoGordon J Freeman
Jun 28, 2014·International Journal of Oncology·Andrew J SandersWen G Jiang
Aug 1, 2014·Neoplasia : an International Journal for Oncology Research·Catherine E GatzaGerard C Blobe
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal

❮ Previous
Next ❯

Citations

Jun 11, 2020·Cancers·Mariacarmela SantarpiaRafael Rosell
Aug 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xueda HuJin Li
Feb 13, 2019·Physiological Reports·Peter Rotwein
Apr 3, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·John B Pawlak, Gerard C Blobe
May 20, 2021·Seminars in Immunology·Kristen E PaukenGordon J Freeman

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
fluorescence activated cell sorting
flow cytometry
PCR
RNAseq2
Assay
protein assay
transfection

Software Mentioned

Beacon Designer
Typer
Image J
SPSS
Sequenom EpiDesigner
Sequenom

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Biophysics of Adhesion

Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. It is also essential for infectious organisms, such as bacteria or viruses, to cause diseases. Understanding the biophysics of cell adhesion can help understand these diseases. Discover the latest research on the biophysics of adhesion here.

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.