BMP-4 enhances epithelial mesenchymal transition and cancer stem cell properties of breast cancer cells via Notch signaling

Choi, Sanghyuk; Yu, Jinyeong; Park, Aran; Dubon, Maria Jose; Do, Jungbeom; Kim, Young-Jae; Nam, Dong Hyun; Noh, Jinok; Park, Ki‐Sook

doi:10.1038/s41598-019-48190-5

Cited by 53 publications

(47 citation statements)

References 56 publications

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“…200 In addition, KLF4 and BMP4 also increase Notch1 and Jagged 1 in breast CSCs to regulate cell migration and invasion. 201,202 BRCA1 is a key regulator of breast cancer cell differentiation; however, it is localized to a conserved intronic enhancer region within the Notch ligand Jagged 1 gene to maintain the stemness of breast CSCs. 203 Similarly, increased Gli3 also promotes cell proliferation and invasion in oral SCC by increasing Notch2.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,233

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,233

998

View full text Add to dashboard Cite

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“… 72 Dll4–Notch integration triggers modulated angiocrine secretion of Noggin by ECs, which is an antagonist of growth factors collectively known as BMPs. 73 Therefore, Noggin regulates the recruitment and differentiation of osteoprogenitor cells, thus promoting bone formation and accelerating the hypertrophy and maturation of chondrocytes in the adjacent growth plate. 74 Ramasamy et al once conducted a study on mice with an EC-specific deficiency of Fbxw7 (which mediates polyubiquitination and proteasomal degradation of active Notch); these mice were characterized by overactivation of Notch in ECs.…”

Section: Coupling Of Osteogenesis and Angiogenesismentioning

confidence: 99%

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Chen

Huang

et al. 2021

Bone Res

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Angiogenesis and osteogenesis are coupled. However, the cellular and molecular regulation of these processes remains to be further investigated. Both tissues have recently been recognized as endocrine organs, which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues. This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature. In addition, research progress related to the bone vasculature, vessel-related skeletal diseases, pathological conditions, and angiogenesis-targeted therapeutic strategies are also summarized. With respect to future perspectives, new techniques such as single-cell sequencing, which can be used to show the cellular diversity and plasticity of both tissues, are facilitating progress in this field. Moreover, extracellular vesicle-mediated nuclear acid communication deserves further investigation. In conclusion, a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.

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“…Likewise, the emergence of CSC properties, which are often defined experimentally as using tumorsphere- or tumor-initiating assays, frequently occur concomitantly with a mesenchymal phenotype [156,157,158,159,160,161,162,163]. STAT3 has been identified as an essential driver of the de novo reprogramming to a CSC state through activation of Sox2, Nanog, and Oct4 [164,165,166,167,168,169,170].…”

Section: Stat3 Activation Of a Mesenchymal/csc Program In Cancer Cmentioning

confidence: 99%

Balancing STAT Activity as a Therapeutic Strategy

Polak

Chernosky

Smigiel

et al. 2019

Cancers

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Driven by dysregulated IL-6 family member cytokine signaling in the tumor microenvironment (TME), aberrant signal transducer and activator of transcription (STAT3) and (STAT5) activation have been identified as key contributors to tumorigenesis. Following transformation, persistent STAT3 activation drives the emergence of mesenchymal/cancer-stem cell (CSC) properties, important determinants of metastatic potential and therapy failure. Moreover, STAT3 signaling within tumor-associated macrophages and neutrophils drives secretion of factors that facilitate metastasis and suppress immune cell function. Persistent STAT5 activation is responsible for cancer cell maintenance through suppression of apoptosis and tumor suppressor signaling. Furthermore, STAT5-mediated CD4+/CD25+ regulatory T cells (Tregs) have been implicated in suppression of immunosurveillance. We discuss these roles for STAT3 and STAT5, and weigh the attractiveness of different modes of targeting each cancer therapy. Moreover, we discuss how anti-tumorigenic STATs, including STAT1 and STAT2, may be leveraged to suppress the pro-tumorigenic functions of STAT3/STAT5 signaling.

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BMP-4 enhances epithelial mesenchymal transition and cancer stem cell properties of breast cancer cells via Notch signaling

Cited by 53 publications

References 56 publications

Targeting cancer stem cell pathways for cancer therapy

Targeting cancer stem cell pathways for cancer therapy

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Balancing STAT Activity as a Therapeutic Strategy

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