The Dual Role of Bone Morphogenetic Proteins in Cancer

Bach, Duc-Hiep; Park, Hyen Joo; Lee, Sang Kook

doi:10.1016/j.omto.2017.10.002

Cited by 153 publications

(141 citation statements)

References 136 publications

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“…Many processes, such as cell differentiation, early development, and tumor growth, are also dependent on BMP signaling 13 . Wang et al 20 .…”

Section: Introductionmentioning

confidence: 99%

“…recently reported that activation of the BMP-BMP receptor (BMPR) pathway conferred resistance to EGFR-TKIs in lung cancer patients harboring EGFR mutations. We have also recently addressed the role of BMPs in cancer, and we have emphasized their function in association with miRNAs, drug resistance, and mutations 13 . Recent studies have also suggested the possibility that small-molecule BMP4 antagonists, such as LDN-193189, were able to effectively inhibit the growth of lung cancer cells and chemotherapy-resistant cancer cells 20, 21…”

Section: Introductionmentioning

confidence: 99%

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BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells

Bach

Luu

Kim

et al. 2018

Molecular Therapy - Nucleic Acids

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Lung cancer is the leading cause of cancer-associated deaths worldwide. In particular, non-small-cell lung cancer (NSCLC) cells harboring epidermal growth factor receptor (EGFR) mutations are associated with resistance development of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. Recent findings suggest that bone morphogenetic proteins (BMPs) and microRNAs (miRNAs) might act as oncogenes or tumor suppressors in the tumor microenvironment. In this study, for the first time, we identified the potential roles of BMPs and miRNAs involved in EGFR-TKI resistance by analyzing datasets from a pair of parental cells and NSCLC cells with acquired EGFR-TKI resistance. BMP4 was observed to be significantly overexpressed in the EGFR-TKI-resistant cells, and its mechanism of action was strongly associated with the induction of cancer cell energy metabolism through the modulation of Acyl-CoA synthetase long-chain family member 4. In addition, miR-139-5p was observed to be significantly downregulated in the resistant NSCLC cells. The combination of miR-139-5p and yuanhuadine, a naturally derived antitumor agent, synergistically suppressed BMP4 expression in the resistant cells. We further confirmed that LDN-193189, a small molecule BMP receptor 1 inhibitor, effectively inhibited tumor growth in a xenograft nude mouse model implanted with the EFGR-TKI-resistant cells. These findings suggest a novel role of BMP4-mediated tumorigenesis in the progression of acquired drug resistance in EGFR-mutant NSCLC cells.

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“…Many processes, such as cell differentiation, early development, and tumor growth, are also dependent on BMP signaling 13 . Wang et al 20 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells

Bach

Luu

Kim

et al. 2018

Molecular Therapy - Nucleic Acids

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“…This is not surprising since it has been reported that other molecules have dual roles and can act as anti-tumoral and/or pro-tumoral factors. For example, the bone morphogenetic proteins (BMPs) that are part of the transforming growth factor-β (TGF-β) superfamily have been related to the induction of angiogenesis, EMT, cancer stem cells (CSCs) and metastasis in aggressive breast, skin, and prostate cancer cells lines and tissues 46 . On the other hand, BMP10 which is part of the BMP family suppresses the aggressiveness of prostate cancer cells by the induction of apoptosis 47 and in patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal subtype 48 .…”

Section: Discussionmentioning

confidence: 99%

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

Hassan

Rutsch

Győrffy

et al. 2020

Sci Rep

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In several carcinomas, the SET Domain Containing 3, Actin Histidine Methyltransferase (SETD3)is associated with oncogenesis. However, there is little knowledge about the role of SETD3 in the progression and prognosis of breast cancer. In this study, we first analyzed the prognostic value of SETD3 in breast cancer patients using the database of the public Kaplan-Meier plotter. Moreover, in vitro assays were performed to assess the role of SETD3 in the viability and capacity of invasion of human breast cancer cell lines. We observed that the high expression of SETD3 was associated with better relapse-free survival (RFS) of the whole collective of 3,951 patients, of Estrogen Receptorpositive, and of Luminal A-type breast cancer patients. However, in patients lacking expression of estrogen-, progesterone-and HER2-receptor, and those affected by a p53-mutation, SETD3 was associated with poor RFS. In vitro analysis showed that SETD3 siRNA depletion affects the viability of triple-negative cells as well as the cytoskeletal function and capacity of invasion of highly invasive MDA-MB-231 cells. Interestingly, SETD3 regulates the expression of other genes associated with cancer such as β-actin, FOXM1, FBXW7, Fascin, eNOS, and MMP-2. Our study suggests that SETD3 expression can act as a subtype-specific biomarker for breast cancer progression and prognosis.MTT proliferation assay. SETD3 depleted cells or controls (5 × 10 3 ) were plated in 96-well plates with DMEM medium (without phenol red) (Gibco ® , cat. No. 31053028, Germany) with FCS and incubated for 96 hours. After the incubation time, the medium was removed completely and cells were incubated with 20 µl/well of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) (cat. No. M2128-1G), at 5 mg/ml for 4 hours, at 37 °C. Subsequently, 100 µl of Stopping buffer, pH 4.7 composed of 10% (w/v) sodium dodecyl sulfate (SDS) (cat. No. 3599286) and 50% (v/v) N,) was added to stop the reaction and dissolve the formazan crystals. The absorbance was measured in a VersaMax ® Microplate Reader (Molecular Devices, Sunnyvale, CA, USA) at a wavelength of 595 nm. The proliferation of the control cells was defined as 100%. Results were derived from three independent sets of triplicate experiments. MTT, SDS, and N,N-Dimethyl formamide were from Sigma-

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“…Despite that, starting from 2006, independent research groups started reporting complications associated with the use of rhBMP-2. The side effects ranged from seroma formation [33,34], ectopic bone growth [35][36][37], osteolysis [38,39], and increased risk of cancer [40,41]. This led to a systematic review and meta-analysis, which was reported in Annals of Internal Medicine in June 2013.…”

Section: Bone Morphogenic Proteinsmentioning

confidence: 99%

Application of Bone Substitutes and Its Future Prospective in Regenerative Medicine

Dahiya¹,

Mishra²,

Bano³

2019

Biomaterial-Supported Tissue Reconstruction or Regeneration

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Bone is a hard and dense connective tissue that supports and maintains the body structure and functions. Several factors like aging, drugs, hormonal changes, and physical activities lead to several kinds of bone injuries/fracture. To address these problems, autologous bone graft is considered an ideal material. However, limited availability and complications related to its harvesting process like donor site morbidity and pain limit the use of autologous bone graft in bone regeneration. With increasing advances in technology, several bone substitute materials such as synthetics, bioceramics, and polymers are emerging as a substitute of auto-or allogenous bone for the treatment of bone defect. These bone substitute materials should be biocompatible, bioresorbable, osteoconductive, osteoinductive, and support the ingrowth of new bone. In this chapter, we summarize the currently available bone graft and bone substitute materials including biological and bio-inorganic factors. An overview of the associated advantages, challenges, and future perspectives to clinical implication is also discussed.

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The Dual Role of Bone Morphogenetic Proteins in Cancer

Cited by 153 publications

References 136 publications

BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells

BMP4 Upregulation Is Associated with Acquired Drug Resistance and Fatty Acid Metabolism in EGFR-Mutant Non-Small-Cell Lung Cancer Cells

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

Application of Bone Substitutes and Its Future Prospective in Regenerative Medicine

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