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Sundqvist, Anders
Publikationer (10 of 13) Visa alla publikationer
Raykova, D., Kermpatsou, D., Malmqvist, T., Harrison, P. J., Rubin Sander, M., Stiller, C., . . . Söderberg, O. (2022). A method for Boolean analysis of protein interactions at a molecular level. Nature Communications, 13(1), Article ID 4755.
Öppna denna publikation i ny flik eller fönster >>A method for Boolean analysis of protein interactions at a molecular level
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2022 (Engelska)Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 13, nr 1, artikel-id 4755Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Determination of interactions between native proteins in cells is important for understanding function. Here the authors report MolBoolean as a method to detect interactions between endogenous proteins in subcellular compartments, using antibody-DNA conjugates for identification and signal amplification. Determining the levels of protein-protein interactions is essential for the analysis of signaling within the cell, characterization of mutation effects, protein function and activation in health and disease, among others. Herein, we describe MolBoolean - a method to detect interactions between endogenous proteins in various subcellular compartments, utilizing antibody-DNA conjugates for identification and signal amplification. In contrast to proximity ligation assays, MolBoolean simultaneously indicates the relative abundances of protein A and B not interacting with each other, as well as the pool of A and B proteins that are proximal enough to be considered an AB complex. MolBoolean is applicable both in fixed cells and tissue sections. The specific and quantifiable data that the method generates provide opportunities for both diagnostic use and medical research.

Ort, förlag, år, upplaga, sidor
Springer Nature, 2022
Nationell ämneskategori
Biokemi och molekylärbiologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
urn:nbn:se:uu:diva-482674 (URN)10.1038/s41467-022-32395-w (DOI)000840338100011 ()35963857 (PubMedID)
Forskningsfinansiär
Stiftelsen för strategisk forskning (SSF)CancerfondenVetenskapsrådet
Anmärkning

Correction in: Nature Communications volume 14, Article number: 5450 (2023)

DOI: 10.1038/s41467-023-41325-3

Tillgänglig från: 2022-09-20 Skapad: 2022-09-20 Senast uppdaterad: 2023-10-24Bibliografiskt granskad
Lind, T., Melo, F. R., Gustafson, A.-M., Sundqvist, A., Zhao, X. O., Moustakas, A., . . . Pejler, G. (2022). Mast cell chymase has a negative impact on human osteoblasts. Matrix Biology, 112, 1-19
Öppna denna publikation i ny flik eller fönster >>Mast cell chymase has a negative impact on human osteoblasts
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2022 (Engelska)Ingår i: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 112, s. 1-19Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Mast cells have been linked to osteoporosis and bone fractures, and in a previous study we found that mice lacking a major mast cell protease, chymase, develop increased diaphyseal bone mass. These findings introduce the possibility that mast cell chymase can regulate bone formation, but the underlying mechanism(s) has not previously been investigated. Here we hypothesized that chymase might exert such effects through a direct negative impact on osteoblasts, i.e., the main bone-building cells. Indeed, we show that chymase has a distinct impact on human primary osteoblasts. Firstly, chymase was shown to have pronounced effects on the morphological features of osteoblasts, including extensive cell contraction and actin reorganization. Chymase also caused a profound reduction in the output of collagen from the osteoblasts, and was shown to degrade osteoblast-secreted fibronectin and to activate pro-matrix metallopeptidase-2 released by the osteoblasts. Further, chymase was shown to have a preferential impact on the gene expression, protein output and phosphorylation status of TGF beta-associated signaling molecules. A transcriptomic analysis was conducted and revealed a significant effect of chymase on several genes of importance for bone metabolism, including a reduction in the expression of osteoprotegerin, which was confirmed at the protein level. Finally, we show that chymase interacts with human osteoblasts and is taken up by the cells. Altogether, the present findings provide a functional link between mast cell chymase and osteoblast function, and can form the basis for a further evaluation of chymase as a potential target for intervention in metabolic bone diseases.

Ort, förlag, år, upplaga, sidor
Elsevier, 2022
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
urn:nbn:se:uu:diva-484746 (URN)10.1016/j.matbio.2022.07.005 (DOI)000848284800002 ()35908613 (PubMedID)
Forskningsfinansiär
VetenskapsrådetCancerfondenHjärt-LungfondenKnut och Alice Wallenbergs Stiftelse
Tillgänglig från: 2022-09-16 Skapad: 2022-09-16 Senast uppdaterad: 2022-09-16Bibliografiskt granskad
Sundqvist, A., Vasilaki, E., Voytyuk, O., Bai, Y., Morikawa, M., Moustakas, A., . . . van Dam, H. (2020). TGF beta and EGF signaling orchestrates the AP-1-and p63 transcriptional regulation of breast cancer invasiveness. Oncogene, 39(22), 4436-4449
Öppna denna publikation i ny flik eller fönster >>TGF beta and EGF signaling orchestrates the AP-1-and p63 transcriptional regulation of breast cancer invasiveness
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2020 (Engelska)Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 39, nr 22, s. 4436-4449Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Activator protein (AP)-1 transcription factors are essential elements of the pro-oncogenic functions of transforming growth factor-beta (TGF beta)-SMAD signaling. Here we show that in multiple HER2+ and/or EGFR+ breast cancer cell lines these AP-1-dependent tumorigenic properties of TGF beta critically rely on epidermal growth factor receptor (EGFR) activation and expression of the Delta N isoform of transcriptional regulator p63. EGFR and Delta Np63 enabled and/or potentiated the activation of a subset of TGF beta-inducible invasion/migration-associated genes, e.g., ITGA2, LAMB3, and WNT7A/B, and enhanced the recruitment of SMAD2/3 to these genes. The TGF beta- and EGF-induced binding of SMAD2/3 and JUNB to these gene loci was accompanied by p63-SMAD2/3 and p63-JUNB complex formation. p63 and EGFR were also found to strongly potentiate TGF beta induction of AP-1 proteins and, in particular, FOS family members. Ectopic overexpression of FOS could counteract the decrease in TGF beta-induced gene activation after p63 depletion. p63 is also involved in the transcriptional regulation of heparin binding (HB)-EGF and EGFR genes, thereby establishing a self-amplification loop that facilitates and empowers the pro-invasive functions of TGF beta. These cooperative pro-oncogenic functions of EGFR, AP-1, p63, and TGF beta were efficiently inhibited by clinically relevant chemical inhibitors. Our findings may, therefore, be of importance for therapy of patients with breast cancers with an activated EGFR-RAS-RAF pathway.

Ort, förlag, år, upplaga, sidor
NATURE PUBLISHING GROUP, 2020
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:uu:diva-423816 (URN)10.1038/s41388-020-1299-z (DOI)000529589900002 ()32350443 (PubMedID)
Forskningsfinansiär
Cancerfonden, 2016/468Cancerfonden, 2018/439Vetenskapsrådet, 2015-02757EU, Europeiska forskningsrådet, 787472
Tillgänglig från: 2020-10-29 Skapad: 2020-10-29 Senast uppdaterad: 2020-10-29Bibliografiskt granskad
Sundqvist, A., Voytyuk, O., Hamdi, M., Popeijus, H. E., Bijlsma-van der Burgt, C., Janssen, J., . . . van Dam, H. (2019). JNK-Dependent cJun Phosphorylation Mitigates TGF beta- and EGF-Induced Pre-Malignant Breast Cancer Cell Invasion by Suppressing AP-1-Mediated Transcriptional Responses. CELLS, 8(12), Article ID 1481.
Öppna denna publikation i ny flik eller fönster >>JNK-Dependent cJun Phosphorylation Mitigates TGF beta- and EGF-Induced Pre-Malignant Breast Cancer Cell Invasion by Suppressing AP-1-Mediated Transcriptional Responses
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2019 (Engelska)Ingår i: CELLS, E-ISSN 2073-4409, Vol. 8, nr 12, artikel-id 1481Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Transforming growth factor-beta (TGF beta) has both tumor-suppressive and tumor-promoting effects in breast cancer. These functions are partly mediated through Smads, intracellular transcriptional effectors of TGF beta. Smads form complexes with other DNA-binding transcription factors to elicit cell-type-dependent responses. Previously, we found that the collagen invasion and migration of pre-malignant breast cancer cells in response to TGF beta and epidermal growth factor (EGF) critically depend on multiple Jun and Fos components of the activator protein (AP)-1 transcription factor complex. Here we report that the same process is negatively regulated by Jun N-terminal kinase (JNK)-dependent cJun phosphorylation. This was demonstrated by analysis of phospho-deficient, phospho-mimicking, and dimer-specific cJun mutants, and experiments employing a mutant version of the phosphatase MKP1 that specifically inhibits JNK. Hyper-phosphorylation of cJun by JNK strongly inhibited its ability to induce several Jun/Fos-regulated genes and to promote migration and invasion. These results show that MEK-AP-1 and JNK-phospho-cJun exhibit distinct pro- and anti-invasive functions, respectively, through differential regulation of Smad- and AP-1-dependent TGF beta target genes. Our findings are of importance for personalized cancer therapy, such as for patients suffering from specific types of breast tumors with activated EGF receptor-Ras or inactivated JNK pathways.

Ort, förlag, år, upplaga, sidor
MDPI, 2019
Nyckelord
invasion, JNK, cJun, TGF beta, AP-1, MAPK, signaling
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:uu:diva-405350 (URN)10.3390/cells8121481 (DOI)000506643500011 ()31766464 (PubMedID)
Forskningsfinansiär
Cancerfonden, 2016/468Cancerfonden, 2015/445Vetenskapsrådet, 2015-02757EU, Europeiska forskningsrådet, 787472
Tillgänglig från: 2020-02-28 Skapad: 2020-02-28 Senast uppdaterad: 2020-02-28Bibliografiskt granskad
Sundqvist, A., Morikawa, M., Ren, J., Vasilaki, E., Kawasaki, N., Kobayashi, M., . . . ten Dijke, P. (2018). JUNB governs a feed-forward network of TGF beta signaling that aggravates breast cancer invasion. Nucleic Acids Research, 46(3), 1180-1195
Öppna denna publikation i ny flik eller fönster >>JUNB governs a feed-forward network of TGF beta signaling that aggravates breast cancer invasion
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2018 (Engelska)Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 46, nr 3, s. 1180-1195Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

It is well established that transforming growth factor-beta (TGF beta) switches its function from being a tumor suppressor to a tumor promoter during the course of tumorigenesis, which involves both cell-intrinsic and environment-mediated mechanisms. We are interested in breast cancer cells, in which SMAD mutations are rare and interactions between SMAD and other transcription factors define pro-oncogenic events. Here, we have performed chromatin immunoprecipitation (ChIP)-sequencing analyses which indicate that the genome-wide landscape of SMAD2/3 binding is altered after prolonged TGF beta stimulation. De novo motif analyses of the SMAD2/3 binding regions predict enrichment of binding motifs for activator protein (AP) 1 in addition to SMAD motifs. TGF beta-induced expression of the AP1 component JUNB was required for expression of many late invasion-mediating genes, creating a feed-forward regulatory network. Moreover, we found that several components in the WNT pathway were enriched among the late TGF beta-target genes, including the invasion-inducing WNT7 proteins. Consistently, overexpression of WNT7A or WNT7B enhanced and potentiated TGF beta-induced breast cancer cell invasion, while inhibition of the WNT pathway reduced this process. Our study thereby helps to explain how accumulation of pro-oncogenic stimuli switches and stabilizes TGF beta-induced cellular phenotypes of epithelial cells.

Ort, förlag, år, upplaga, sidor
OXFORD UNIV PRESS, 2018
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:uu:diva-349356 (URN)10.1093/nar/gkx1190 (DOI)000425294400020 ()29186616 (PubMedID)
Forskningsfinansiär
Cancerfonden, 09 0773, 10 0452, 2016/445Vetenskapsrådet, 2015-02757
Tillgänglig från: 2018-05-02 Skapad: 2018-05-02 Senast uppdaterad: 2022-01-29Bibliografiskt granskad
Morikawa, M., Koinuma, D., Mizutani, A., Kawasaki, N., Holmborn, K., Sundqvist, A., . . . Miyazono, K. (2016). BMP Sustains Embryonic Stem Cell Self-Renewal through Distinct Functions of Different Kruppel-like Factors. Stem Cell Reports, 6(1), 64-73
Öppna denna publikation i ny flik eller fönster >>BMP Sustains Embryonic Stem Cell Self-Renewal through Distinct Functions of Different Kruppel-like Factors
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2016 (Engelska)Ingår i: Stem Cell Reports, ISSN 2213-6711, Vol. 6, nr 1, s. 64-73Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Bone morphogenetic protein (BMP) signaling exerts paradoxical roles in pluripotent stem cells (PSCs); it sustains self-renewal of mouse embryonic stem cells (ESCs), while it induces differentiation in other PSCs, including human ESCs. Here, we revisit the roles of BMP-4 using mouse ESCs (mESCs) in naive and primed states. SMAD1 and SMAD5, which transduce BMP signals, recognize enhancer regions together with KLF4 and KLF5 in naive mESCs. KLF4 physically interacts with SMAD1 and suppresses its activity. Consistently, a subpopulation of cells with active BMP-SMAD can be ablated without disturbing the naive state of the culture. Moreover, Smad1/5 double-knockout mESCs stay in the naive state, indicating that the BMP-SMAD pathway is dispensable for it. In contrast, the MEK5-ERK5 pathway mediates BMP-4-induced self-renewal of mESCs by inducing Klf2, a critical factor for the ground state pluripotency. Our study illustrates that BMP exerts its self-renewing effect through distinct functions of different Kruppel-like factors.

Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
urn:nbn:se:uu:diva-276812 (URN)10.1016/j.stemcr.2015.12.004 (DOI)000368099500008 ()26771354 (PubMedID)
Forskningsfinansiär
Cancerfonden, 100452
Tillgänglig från: 2016-02-16 Skapad: 2016-02-16 Senast uppdaterad: 2022-01-29Bibliografiskt granskad
Carthy, J. M., Sundqvist, A., Heldin, A., Van Dam, H., Kletsas, D., Heldin, C.-H. & Moustakas, A. (2015). Tamoxifen Inhibits TGF-beta-Mediated Activation of Myofibroblasts by Blocking Non-Smad Signaling Through ERK1/2. Journal of Cellular Physiology, 230(12), 3084-3092
Öppna denna publikation i ny flik eller fönster >>Tamoxifen Inhibits TGF-beta-Mediated Activation of Myofibroblasts by Blocking Non-Smad Signaling Through ERK1/2
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2015 (Engelska)Ingår i: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 230, nr 12, s. 3084-3092Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine which stimulates the differentiation of fibroblasts into myofibroblasts. Myofibroblasts are critical for normal wound healing, but also accumulate pathologically in a number of chronic inflammatory conditions where they are key contributors to aberrant tissue remodeling and fibrosis, and in cancer stroma. In the current study, we identified a role for tamoxifen as a potent inhibitor of the TGF-beta-mediated activation of primary human skin and breast fibroblasts. Our data indicate that tamoxifen does not interfere with canonical Smad signaling downstream of TGF-beta but rather blocks non-Smad signaling through ERK1/2 MAP-kinase and the AP-1 transcription factor FRA2. We further demonstrate by siRNA-mediated knockdown that FRA2 is critical for the induced expression of myogenic proteins in response to TGF-beta. Functionally, TGF-beta-stimulated fibroblast-mediated contraction of collagen gels was impaired in the presence of tamoxifen. Altogether, these data demonstrate that tamoxifen prevents myofibroblast differentiation and, therefore, may provide therapeutic benefits to patients suffering from chronic inflammatory conditions or cancer.

Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Cancer och onkologi
Identifikatorer
urn:nbn:se:uu:diva-262938 (URN)10.1002/jcp.25049 (DOI)000360378000026 ()26096876 (PubMedID)
Forskningsfinansiär
Cancerfonden, CAN 2006/1078 CAN 2009/900 CAN 2012/438Vetenskapsrådet, K2007-66X-14936-04-3 K2010-67X-14936-07-3 K2013-66X-14936-10-5
Tillgänglig från: 2015-10-02 Skapad: 2015-09-23 Senast uppdaterad: 2017-12-01Bibliografiskt granskad
Sundqvist, A., Zieba, A., Vasilaki, E., Herrera Hidalgo, C., Söderberg, O., Koinuma, D., . . . van Dam, H. (2013). Specific interactions between Smad proteins and AP-1 components determine TGFβ-induced breast cancer cell invasion. Oncogene, 32(31), 3606-3615
Öppna denna publikation i ny flik eller fönster >>Specific interactions between Smad proteins and AP-1 components determine TGFβ-induced breast cancer cell invasion
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2013 (Engelska)Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 32, nr 31, s. 3606-3615Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Deregulation of the transforming growth factor β (TGFβ) signal transduction cascade is functionally linked to cancer. In early phases, TGFβ acts as a tumor suppressor by inhibiting tumor cell proliferation, whereas in late phases, it can act as a tumor promoter by stimulating tumor cell invasion and metastasis. Smad transcriptional effectors mediate TGFβ responses, but relatively little is known about the Smad-containing complexes that are important for epithelial-mesenchymal transition and invasion. In this study, we have tested the hypothesis that specific members of the AP-1 transcription factor family determine TGFβ signaling specificity in breast cancer cell invasion. Using a 3D model of collagen-embedded spheroids of MCF10A-MII premalignant human breast cancer cells, we identified the AP-1 transcription factor components c-Jun, JunB, c-Fos and Fra1 as essential factors for TGFβ-induced invasion and found that various mesenchymal and invasion-associated TGFβ-induced genes are co-regulated by these proteins. In situ proximity ligation assays showed that TGFβ signaling not only induces complexes between Smad3 and Smad4 in the nucleus but also complexes between Smad2/3 and Fra1, whereas complexes between Smad3, c-Jun and JunB could already be detected before TGFβ stimulation. Finally, chromatin immunoprecipitations showed that c-Jun, JunB and Fra1, but not c-Fos, are required for TGFβ-induced binding of Smad2/3 to the mmp-10 and pai-1 promoters. Together these results suggest that in particular formation of Smad2/3-Fra1 complexes may reflect activation of the Smad/AP-1-dependent TGFβ-induced invasion program.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:uu:diva-180124 (URN)10.1038/onc.2012.370 (DOI)000322638400005 ()22926518 (PubMedID)
Anmärkning

Agata Zieba & Eleftheria Vasilaki contributed equally to this work.

Tillgänglig från: 2012-08-30 Skapad: 2012-08-30 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
Lind, T., Sundqvist, A., Hu, L., Pejler, G., Andersson, G., Jacobson, A. & Melhus, H. (2013). Vitamin A Is a Negative Regulator of Osteoblast Mineralization. PLOS ONE, 8(12), e82388
Öppna denna publikation i ny flik eller fönster >>Vitamin A Is a Negative Regulator of Osteoblast Mineralization
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2013 (Engelska)Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 8, nr 12, s. e82388-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

An excessive intake of vitamin A has been associated with an increased risk of fractures in humans. In animals, a high vitamin A intake leads to a reduction of long bone diameter and spontaneous fractures. Studies in rodents indicate that the bone thinning is due to increased periosteal bone resorption and reduced radial growth. Whether the latter is a consequence of direct effects on bone or indirect effects on appetite and general growth is unknown. In this study we therefore used pair-feeding and dynamic histomorphometry to investigate the direct effect of a high intake of vitamin A on bone formation in rats. Although there were no differences in body weight or femur length compared to controls, there was an approximately halved bone formation and mineral apposition rate at the femur diaphysis of rats fed vitamin A. To try to clarify the mechanism(s) behind this reduction, we treated primary human osteoblasts and a murine preosteoblastic cell line (MC3T3-E1) with the active metabolite of vitamin A; retinoic acid (RA), a retinoic acid receptor (RAR) antagonist (AGN194310), and a Cyp26 inhibitor (R115866) which blocks endogenous RA catabolism. We found that RA, via RARs, suppressed in vitro mineralization. This was independent of a negative effect on osteoblast proliferation. Alkaline phosphatase and bone gamma carboxyglutamate protein (Bglap, Osteocalcin) were drastically reduced in RA treated cells and RA also reduced the protein levels of Runx2 and Osterix, key transcription factors for progression to a mature osteoblast. Normal osteoblast differentiation involved up regulation of Cyp26b1, the major enzyme responsible for RA degradation, suggesting that a drop in RA signaling is required for osteogenesis analogous to what has been found for chondrogenesis. In addition, RA decreased Phex, an osteoblast/osteocyte protein necessary for mineralization. Taken together, our data indicate that vitamin A is a negative regulator of osteoblast mineralization.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:uu:diva-217667 (URN)10.1371/journal.pone.0082388 (DOI)000328707400074 ()
Tillgänglig från: 2014-02-05 Skapad: 2014-02-04 Senast uppdaterad: 2021-06-14Bibliografiskt granskad
Naber, H. P., Wiercinska, E., Pardali, E., van Laar, T., Nirmala, E., Sundqvist, A., . . . ten Dijke, P. (2012). BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β(3) expression. Cellular Oncology, 35(1), 19-28
Öppna denna publikation i ny flik eller fönster >>BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β(3) expression
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2012 (Engelska)Ingår i: Cellular Oncology, ISSN 2211-3428, E-ISSN 2211-3436, Vol. 35, nr 1, s. 19-28Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: The transforming growth factor (TGF)-β superfamily comprises cytokines such as TGF-β and Bone Morphogenetic Proteins (BMPs), which have a critical role in a multitude of biological processes. In breast cancer, high levels of TGF-β are associated with poor outcome, whereas inhibition of TGF-β-signaling reduces metastasis. In contrast, BMP-7 inhibits bone metastasis of breast cancer cells.

METHODS: In this study, we investigated the effect of BMP-7 on TGF-β-induced invasion in a 3 dimensional invasion assay.

RESULTS: BMP-7 inhibited TGF-β-induced invasion of the metastatic breast cancer cell line MCF10CA1a, but not of its premalignant precursor MCF10AT in a spheroid invasion model. The inhibitory effect appears to be specific for BMP-7, as its closest homolog, BMP-6, did not alter the invasion of MCF10CA1a spheroids. To elucidate the mechanism by which BMP-7 inhibits TGF-β-induced invasion, we analyzed invasion-related genes. BMP-7 inhibited TGF-β-induced expression of integrin α(v)β(3) in the spheroids. Moreover, targeting of integrins by a chemical inhibitor or knockdown of integrin β(3) negatively affected TGF-β-induced invasion. On the other hand, overexpression of integrin β(3) counteracted the inhibitory effect of BMP7 on TGF-β-induced invasion.

CONCLUSION: Thus, BMP-7 may exert anti-invasive actions by inhibiting TGF-β-induced expression of integrin β(3).

Ort, förlag, år, upplaga, sidor
Springer, 2012
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:uu:diva-168807 (URN)10.1007/s13402-011-0058-0 (DOI)000299920300003 ()21935711 (PubMedID)
Tillgänglig från: 2012-02-15 Skapad: 2012-02-15 Senast uppdaterad: 2017-12-07Bibliografiskt granskad
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