Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling

Li, Jin; Ye, Lin; Sanders, Andrew; Jiang, Wen Guo

doi:10.1002/jcb.24128

Cited by 37 publications

(38 citation statements)

References 26 publications

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“…Alterations, following RGMb knockdown, were observed in the regulation of c-myc, caspase-3, SNAIL, TWIST, FAK and paxillin. This study also implicated RGMb knockdown to contribute to the Smad-dependent pathway, enhancing levels of activated Smad 1 and 3 in untreated cells, with greater responses seen following BMP-7 treatment and a switching to Smad 1 activation following inhibition of Smad 3, whereas phosphorylation of JNK, ILP and TAK was inhibited following RGMb knockdown suggesting suppression of the Smad-independent pathway (22).…”

Section: Discussionmentioning

confidence: 93%

“…Further work explored the impact of targeting RGMb in breast cancer cell lines in vitro. This study demonstrated a potential role for RGMb in breast cancer proliferation, matrix-adhesion and migration where targeting this molecule enhanced these aggressive traits and implicated links with Smad-dependent and Smad-independent pathways (22). Similarly, RGMb appears to play a role in prostate cancer progression.…”

Section: Introductionmentioning

confidence: 92%

“…The results observed here regarding the role of RGMb in the basic function of endothelial cells are somewhat in line with previous work from our laboratories focusing on breast and prostate cancer. In both of these studies, knockout of RGMb resulted in enhanced migratory rates of prostate (PC-3) and breast (MDA-MB-231, MCF-7) cancer cell lines and enhanced cell growth rates in PC-3 and MDA-MB-231 cells, though not MCF-7 cells (21,22). Together with our results the data suggest RGMb is involved in the regulation of cell migration and growth of certain cancer and to some extent endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…This methodology has been previously reported (23,24). Plasmids containing ribozyme transgenes had previously been developed within the laboratory (21,22). Briefly, ribozyme transgene sequences were designed based on the predicted secondary structure of the RGMb transcript using Zukers RNA Mfold program (25) and were synthesised by Invitrogen (Paisley, UK).…”

Section: Methodsmentioning

confidence: 99%

“…A number of recent studies from our laboratories have explored the importance of the members of the RGM family in breast and prostate cancer (20)(21)(22). RGM levels were examined in a breast cancer cohort in conjunction with clinical pathological patient data.…”

Section: Introductionmentioning

confidence: 99%

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Tumour angiogenesis and repulsive guidance molecule b: A role in HGF- and BMP-7-mediated angiogenesis

Sanders

et al. 2014

International Journal of Oncology

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Abstract. Hepatocyte growth factor (HGF) is a key growth factor linked to promoting cancer progression and angiogenesis. The present study identifies repulsive guidance molecule b (RGMb), a bone morphogenetic protein (BMP) co-receptor, as a gene whose expression is regulated by HGF and explores the potential of RGMb to contribute to the process of angiogenesis. Microarray analysis was used to identify HGF responsive genes in HECV endothelial cells, identifying RGMb. RGMb was subsequently targeted using a ribozyme transgene system and its role in angiogenesis assessed using in vitro and in vivo assays. The importance of RGMb in pro-angiogenic responses to HGF and BMP-7 was also assessed. Microarray analysis identified RGMb as a gene upregulated as a result of HGF treatment. Knockdown of RGMb, in HECV cells, had minimal effects on tubule formation, brought about a general, although non-significant increase in cell growth and enhanced cell migration. Similarly, no significant effect of RGMb knockdown was found in vivo using a co-inoculation angiogenesis model. Knockdown of RGMb was, however, found to reduce the responsiveness of HECV cells to HGF treatment and particularly to BMP-7 treatment in regard to the enhanced migratory and tubule formation brought about by these treatments in vitro. Our results indicate that RGMb expression can be influenced by HGF treatment. Whilst this molecule appears to have minimal impact on angiogenic traits individually, it demonstrates an involvement in propagating pro-angiogenic effects of HGF and particularly BMP-7 and thus, may play a role in regulating angiogenic responses to HGF and BMP-7.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumour angiogenesis and repulsive guidance molecule b: A role in HGF- and BMP-7-mediated angiogenesis

Sanders

et al. 2014

International Journal of Oncology

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RGMb impacts partial epithelial‐mesenchymal transition and BMP2‐Induced ID mRNA expression independent of PD‐L2 in nonsmall cell lung cancer cells

Dorset,

Daugaard,

Larsen

et al. 2023

Cell Biology International

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PD‐1/PD‐ligand‐axis immunotherapy‐mediated activation of T‐cells for cancer cell elimination is a promising treatment of nonsmall cell lung cancer (NSCLC). However, the effect of immunotherapy on intracellular signaling pathways in cancer cells still needs further delineation. Repulsive Guidance Molecule b (RGMb), a regulator of Bone Morphogenetic Proteins (BMPs) signaling, interacts with the PD‐ligand, PD‐L2, at cancer cell membranes. Accordingly, a clarification of the functions of RGMb and its relation to PD‐L2 might provide insight into NSCLC cell signaling responses to PD‐1/PD‐ligand‐axis immunotherapy. In this study, the functions of RGMb and PD‐L2 were examined using the two NSCLC cell lines HCC827 and A549. CRISPR/Cas9 was used to decrease the expression of RGMb and PD‐L2, while lentiviral vectors were used to increase their expression. Downstream effects were examined by RT‐qPCR and immunoassays. Ectopic expression of RGMb impacted BMP2‐induced expression of ID1 and ID2 messenger RNA (mRNA) independently of PD‐L2, while RGMb depletion by CRISPR/Cas9 did not affect the BMP2‐mediated induction of ID1, ID2, and ID3 mRNA. However, depletion of RGMb resulted in a partial epithelial‐mesenchymal transition (EMT) gene expression profile in HCC827 cells, which was not mimicked by PD‐L2 depletion. The results show that RGMb is a coregulator of BMP signaling and hence, ID mRNA expression and that RGMb can control the EMT balance in NSCLC cells. However, RGMb appears to exert these functions independently of PD‐L2, and accordingly, the PD‐1/PD‐ligand axis for immune surveillance in NSCLC cells.

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TGF‐β superfamily co‐receptors in cancer

Pawlak

Blobe

2021

Developmental Dynamics

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Transforming growth factor‐β (TGF‐β) superfamily signaling via their cognate receptors is frequently modified by TGF‐β superfamily co‐receptors. Signaling through SMAD‐mediated pathways may be enhanced or depressed depending on the specific co‐receptor and cell context. This dynamic effect on signaling is further modified by the release of many of the co‐receptors from the membrane to generate soluble forms that are often antagonistic to the membrane‐bound receptors. The co‐receptors discussed here include TβRIII (betaglycan), endoglin, BAMBI, CD109, SCUBE proteins, neuropilins, Cripto‐1, MuSK, and RGMs. Dysregulation of these co‐receptors can lead to altered TGF‐β superfamily signaling that contributes to the pathophysiology of many cancers through regulation of growth, metastatic potential, and the tumor microenvironment. Here we describe the role of several TGF‐β superfamily co‐receptors on TGF‐β superfamily signaling and the impact on cellular and physiological functions with a particular focus on cancer, including a discussion on recent pharmacological advances and potential clinical applications targeting these co‐receptors.

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Repulsive guidance molecule B (RGMB) plays negative roles in breast cancer by coordinating BMP signaling

Cited by 37 publications

References 26 publications

Tumour angiogenesis and repulsive guidance molecule b: A role in HGF- and BMP-7-mediated angiogenesis

Tumour angiogenesis and repulsive guidance molecule b: A role in HGF- and BMP-7-mediated angiogenesis

RGMb impacts partial epithelial‐mesenchymal transition and BMP2‐Induced ID mRNA expression independent of PD‐L2 in nonsmall cell lung cancer cells

TGF‐β superfamily co‐receptors in cancer

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