Bone morphogenetic protein signaling promotes tumorigenesis in a murine model of high-grade glioma

Hover, Laura D.; Owens, Philip; Munden, Alexander; Wang, Jialiang; Chambless, Lola B.; Hopkins, Corey R.; Hong, Charles C.; Moses, Harold L.; Abel, Ty W.

doi:10.1093/neuonc/nov310

Cited by 27 publications

(20 citation statements)

References 36 publications

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“…Steinert et al 33 found through in vitro experiments that: in breast cancer cells with normal nutrition, BMP2 can promote the occurrence of apoptosis by transcription of apoptosis-related genes (such as PKR, EIF2α); in breast cancer cells with malnutrition, BMP2 can generate ID-1 through the MAPK signal transduction pathway and inhibit the activation of Caspase-3 to enhance the viability of breast cancer cells. This phenomenon suggests that there should be some type of cell homeostasis mechanism in the process of tumor morphogenesis to regulate the induction or inhibition mediated by BMP 11 , 34 .…”

Section: Discussionmentioning

confidence: 99%

A new glioma grading model based on histopathology and Bone Morphogenetic Protein 2 mRNA expression

Zhou

Zhao

et al. 2020

Sci Rep

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Glioma, the most common form of primary malignant brain tumors, is graded based solely on histopathological appearance, which has led to prognostic discrepancies. This study aimed to establish a new glioma grading model by analyzing the expression of Bone Morphogenetic Protein 2 (BMP2) mRNA in patients with gliomas as well, named the Histopathological-BMP2 (HB) system. Clinical information was collected from 692 patients from the Chinese Glioma Genome Atlas database. According to pathological glioma subtypes and the expression of BMP2 mRNA in tumor tissues, the new subtypes HBs, HBh, HBm and HB1 were established, with BMP2 expression highest in HBs and lowest in HB1. Survival periods were analyzed. Based on this, the expression of three BMP2 receptors (BMPR1A, BMPR1B, and BMPR2) was also analyzed, which was related to the prognosis of patients. This new classification model was validated in further groups of patients from the CGGA database (n = 291) and the Cancer Genome Atlas (n = 625). A new glioma grade (HB grade) based on histopathology and BMP2 expression can predict the prognosis of glioma patients, with BMPR1B and BMPR2 expression indicating a different prognosis in different types of gliomas. The higher the concentration of BMP2, the better the prognosis of patients.

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Section: Discussionmentioning

confidence: 99%

A new glioma grading model based on histopathology and Bone Morphogenetic Protein 2 mRNA expression

Zhou

Zhao

et al. 2020

Sci Rep

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“…Recently, we demonstrated that BMP signalling is active in the majority of high-grade glioma (HGG) cells obtained from adult patients [55]. Moreover, consistent with a role of BMP signalling in human HGG, deletion of BMPR1A (ALK3) in oncogenic mouse astrocytes resulted in decreased proliferation, invasion and migration.…”

Section: Role Of Bmp Signalling In Cancer Pathogenesismentioning

confidence: 76%

Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition

Jiramongkolchai

Owens

Hong

2016

Biochemical Society Transactions

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Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-β (TGF-β) family signalling pathway. Similar to TGF-β, the complex roles of BMPs in development and disease are demonstrated by their dichotomous roles in various cancers and cancer stages. Although early studies implicated BMP signalling in tumour suppressive phenotypes, the results of more recent experiments recognize BMPs as potent tumour promoters. Many of these complexities are becoming illuminated by understanding the role of BMPs in their contextual role in unique cell types of cancer and the impact of their surrounding tumour microenvironment. Here we review the emerging roles of BMP signalling in cancer, with a focus on the molecular underpinnings of BMP signalling in individual cancers as a valid therapeutic target for cancer prevention and treatment.

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“…Smad4 is also an indispensable element of the bone morphogenetic protein (BMP)-signaling pathway. The BMP signaling pathway has been shown to promote tumorigenesis in a murine model of high-grade glioma (35). In addition, Smad4 protein is highly expressed in glioma; therefore, Smad4 is a crucial target gene in the treatment of glioma.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 inhibits the proliferation of C6 glioma cells by targeting Smad4

Zhang

Gong

et al. 2017

International Journal of Molecular Medicine

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MicroRNA-124 (miR-124) has been shown to be downregulated in glioma; however, its biological functions in glioma are not yet fully understood. The aim of this study was to examine the Smad4‑dependent effects of miR‑124 on C6 glioma cell proliferation. In this study, the level of miR‑124 was found to be enhanced in C6 cells upon transfection with miR‑124 mimics, and the mechanisms of action of miR‑124 in C6 cells were investigated by reverse transcriptase-quantitative polymerase chain reaction, MTT assay, western blot analysis and luciferase reporter assays in vitro. The results revealed that miR‑124 expression was significantly lower in the C6 cells than in either normal rat brain tissue or astrocytes. Upon the overexpression of miR‑124, the proliferation of the C6 cells decreased and Smad4 expression was significantly suppressed. Smad4 was identified as a direct target of miR‑124 through luciferase reporter assays. Furthermore, miR‑124 was found to modulate signal transducer and activator of transcription 3 (Stat3) by downregulating Smad4 expression. Using small interfering RNA targeting Smad4 mRNA, we also confirmed that miR‑124 downregulated c‑Myc by modulating Smad4 expression. In addition, caspase‑3 expression was induced by miR‑124 overexpression, but not via Smad4 downregulation. On the whole, our results demonstrate that miR‑124 upregulation inhibits the growth of C6 glioma cells by targeting Smad4 directly. These findings may be clinically useful for the development of therapeutic strategies directed toward miR‑124 function in patients with glioma.

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Bone morphogenetic protein signaling promotes tumorigenesis in a murine model of high-grade glioma

Abstract: BMP inhibition may represent a viable therapeutic approach in adult HGG.

Cited by 27 publications

References 36 publications

A new glioma grading model based on histopathology and Bone Morphogenetic Protein 2 mRNA expression

A new glioma grading model based on histopathology and Bone Morphogenetic Protein 2 mRNA expression

Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition

MicroRNA-124 inhibits the proliferation of C6 glioma cells by targeting Smad4

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