Autocrine BMP-4 Signaling Is a Therapeutic Target in Colorectal Cancer

Yokoyama, Yuichiro; Watanabe, Toshiaki; Tamura, Yusuke; Hashizume, Yoshinobu; Miyazono, Kohei; Ehata, Shogo

doi:10.1158/0008-5472.can-17-0112

Cited by 61 publications

(65 citation statements)

References 47 publications

(59 reference statements)

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“…Immunohistochemistry was carried out as previously described . For the immunostaining of human ccRCC tissues, formalin‐fixed, paraffin‐embedded human clinical samples were collected from patients at The University of Tokyo Hospital after informed consent had been obtained.…”

Section: Methodsmentioning

confidence: 99%

“…Antibodies against c‐Ski (#A303‐518A; Bethyl Laboratories, Montgomery, TX, USA), Noggin (4C9; Sigma‐Aldrich), and HA (3F10; Sigma‐Aldrich) were used as primary antibodies. Other primary antibodies and secondary antibodies were prepared as previously described …”

Section: Methodsmentioning

confidence: 99%

“…We used a lentiviral vector system to overexpress specific genes as previously described. 7 For the overexpression of c-Ski or Noggin, complementary DNAs encoding human SKI or human NOG were inserted into pENTR201 with a multi-cloning site (pENTR201-MCS) empty vector and then transferred to a pCSII-EF-RfA destination vector by Gateway cloning technology (Thermo Fisher Scientific). 8 Introduction of luciferase and HA-tagged dominant-negative TGF-β type II receptor mutant (dnTβRII) was carried out as described previously.…”

Section: Lentiviral Production and Infectionmentioning

confidence: 99%

“…Immunohistochemistry was carried out as previously described. 7 For the immunostaining of human ccRCC tissues, formalin-fixed, paraf- Life Technologies, Carlsbad, CA, USA). TUNEL staining was carried out using the In situ Cell Death Detection Kit (TMR red; Roche Diagnostics, Basel, Switzerland) and DAPI Fluoromount-G (Southern Biotech, Birmingham, AL, USA), as previously described.…”

Section: Immunohistochemistry and Tunel Stainingmentioning

confidence: 99%

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c‐Ski accelerates renal cancer progression by attenuating transforming growth factor β signaling

et al. 2019

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Although transforming growth factor beta ( TGF ‐β) is known to be involved in the pathogenesis and progression of many cancers, its role in renal cancer has not been fully investigated. In the present study, we examined the role of TGF ‐β in clear cell renal carcinoma (cc RCC ) progression in vitro and in vivo. First, expression levels of TGF ‐β signaling pathway components were examined. Microarray and immunohistochemical analyses showed that the expression of c‐Ski, a transcriptional corepressor of Smad‐dependent TGF‐β and bone morphogenetic protein (BMP) signaling, was higher in cc RCC tissues than in normal renal tissues. Next, a functional analysis of c‐Ski effects was carried out. Bioluminescence imaging of renal orthotopic tumor models demonstrated that overexpression of c‐Ski in human cc RCC cells promoted in vivo tumor formation. Enhancement of tumor formation was also reproduced by the introduction of a dominant‐negative mutant TGF ‐β type II receptor into cc RCC cells. In contrast, introduction of the BMP signaling inhibitor Noggin failed to accelerate tumor formation, suggesting that the tumor‐promoting effect of c‐Ski depends on the inhibition of TGF ‐β signaling rather than of BMP signaling. Finally, the molecular mechanism of the tumor‐suppressive role of TGF ‐β was assessed. Although TGF ‐β signaling did not affect tumor angiogenesis, apoptosis of cc RCC cells was induced by TGF ‐β. Taken together, these findings suggest that c‐Ski suppresses TGF ‐β signaling in cc RCC cells, which, in turn, attenuates the tumor‐suppressive effect of TGF ‐β.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Lentiviral Production and Infectionmentioning

confidence: 99%

Section: Immunohistochemistry and Tunel Stainingmentioning

confidence: 99%

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c‐Ski accelerates renal cancer progression by attenuating transforming growth factor β signaling

et al. 2019

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“…Bone morphogenetic protein 4 (BMP4) can abolish cancer stem cell populations in human cancers [27][28][29][30][31][32], including in malignant gliomas [33][34][35][36][37]. In a current phase I clinical trial (NCT02869243) human recombinant BMP4 is being administered through intratumoral and interstitial convection-enhanced delivery (CED) for adult glioblastoma treatment (https://clinicaltrials.gov/ct2/ show/NCT02869243).…”

Section: Introductionmentioning

confidence: 99%

Bone Morphogenetic Protein 4 Targeting Glioma Stem-Like Cells for Malignant Glioma Treatment: Latest Advances and Implications for Clinical Application

Nayak

Mahenthiran

Yang

et al. 2020

Cancers

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Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicates its potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, with an emphasis on pediatric malignant gliomas. We also summarize BMP4 delivery strategies, highlighting biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.

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Neurotensin receptor 1 signaling promotes pancreatic cancer progression

et al. 2020

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Neurotensin (NTS) receptor 1 (NTSR1) is expressed in highly malignant pancreatic cancer cells, which were established by serial orthotopic transplantations. NTS/NTSR1 signaling contributes to the progression of pancreatic cancer through the activation of MAPK and NF‐κB signaling pathways and the induction of the genes related to inflammation. Targeting NTSR1 signaling by SR48692 inhibits pancreatic cancer progression.

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Autocrine BMP-4 Signaling Is a Therapeutic Target in Colorectal Cancer

Cited by 61 publications

References 47 publications

c‐Ski accelerates renal cancer progression by attenuating transforming growth factor β signaling

c‐Ski accelerates renal cancer progression by attenuating transforming growth factor β signaling

Bone Morphogenetic Protein 4 Targeting Glioma Stem-Like Cells for Malignant Glioma Treatment: Latest Advances and Implications for Clinical Application

Neurotensin receptor 1 signaling promotes pancreatic cancer progression

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