Tumor Promoting Effect of BMP Signaling in Endometrial Cancer
The effects of bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, in endometrial cancer (EC) have yet to be determined. In this study, we analyzed the TCGA and MSK-IMPACT datasets and investigated the effects of BMP2 and of TWSG1, a BMP antagonist, on Ish...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/7882 |
| _version_ | 1797525564520660992 |
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| author | Tomohiko Fukuda Risa Fukuda Kohei Miyazono Carl-Henrik Heldin |
| author_facet | Tomohiko Fukuda Risa Fukuda Kohei Miyazono Carl-Henrik Heldin |
| author_sort | Tomohiko Fukuda |
| collection | DOAJ |
| description | The effects of bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, in endometrial cancer (EC) have yet to be determined. In this study, we analyzed the TCGA and MSK-IMPACT datasets and investigated the effects of BMP2 and of TWSG1, a BMP antagonist, on Ishikawa EC cells. Frequent <i>ACVR1</i> mutations and high mRNA expressions of BMP ligands and receptors were observed in EC patients of the TCGA and MSK-IMPACT datasets. Ishikawa cells secreted higher amounts of BMP2 compared with ovarian cancer cell lines. Exogenous BMP2 stimulation enhanced EC cell sphere formation via c-KIT induction. BMP2 also induced EMT of EC cells, and promoted migration by induction of SLUG. The BMP receptor kinase inhibitor LDN193189 augmented the growth inhibitory effects of carboplatin. Analyses of mRNAs of several BMP antagonists revealed that <i>TWSG1</i> mRNA was abundantly expressed in Ishikawa cells. TWSG1 suppressed BMP7-induced, but not BMP2-induced, EC cell sphere formation and migration. Our results suggest that BMP signaling promotes EC tumorigenesis, and that TWSG1 antagonizes BMP7 in EC. BMP signaling inhibitors, in combination with chemotherapy, might be useful in the treatment of EC patients. |
| first_indexed | 2024-03-10T09:14:42Z |
| format | Article |
| id | doaj.art-2202241c88dc4301b175cebbbc8a770f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:14:42Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2202241c88dc4301b175cebbbc8a770f2023-11-22T05:39:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215788210.3390/ijms22157882Tumor Promoting Effect of BMP Signaling in Endometrial CancerTomohiko Fukuda0Risa Fukuda1Kohei Miyazono2Carl-Henrik Heldin3Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Box 582, Uppsala University, SE-751 23 Uppsala, SwedenScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Box 582, Uppsala University, SE-751 23 Uppsala, SwedenScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Box 582, Uppsala University, SE-751 23 Uppsala, SwedenScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Box 582, Uppsala University, SE-751 23 Uppsala, SwedenThe effects of bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) family, in endometrial cancer (EC) have yet to be determined. In this study, we analyzed the TCGA and MSK-IMPACT datasets and investigated the effects of BMP2 and of TWSG1, a BMP antagonist, on Ishikawa EC cells. Frequent <i>ACVR1</i> mutations and high mRNA expressions of BMP ligands and receptors were observed in EC patients of the TCGA and MSK-IMPACT datasets. Ishikawa cells secreted higher amounts of BMP2 compared with ovarian cancer cell lines. Exogenous BMP2 stimulation enhanced EC cell sphere formation via c-KIT induction. BMP2 also induced EMT of EC cells, and promoted migration by induction of SLUG. The BMP receptor kinase inhibitor LDN193189 augmented the growth inhibitory effects of carboplatin. Analyses of mRNAs of several BMP antagonists revealed that <i>TWSG1</i> mRNA was abundantly expressed in Ishikawa cells. TWSG1 suppressed BMP7-induced, but not BMP2-induced, EC cell sphere formation and migration. Our results suggest that BMP signaling promotes EC tumorigenesis, and that TWSG1 antagonizes BMP7 in EC. BMP signaling inhibitors, in combination with chemotherapy, might be useful in the treatment of EC patients.https://www.mdpi.com/1422-0067/22/15/7882endometrial cancerBMPACVR1EMTcancer stem cells |
| spellingShingle | Tomohiko Fukuda Risa Fukuda Kohei Miyazono Carl-Henrik Heldin Tumor Promoting Effect of BMP Signaling in Endometrial Cancer International Journal of Molecular Sciences endometrial cancer BMP ACVR1 EMT cancer stem cells |
| title | Tumor Promoting Effect of BMP Signaling in Endometrial Cancer |
| title_full | Tumor Promoting Effect of BMP Signaling in Endometrial Cancer |
| title_fullStr | Tumor Promoting Effect of BMP Signaling in Endometrial Cancer |
| title_full_unstemmed | Tumor Promoting Effect of BMP Signaling in Endometrial Cancer |
| title_short | Tumor Promoting Effect of BMP Signaling in Endometrial Cancer |
| title_sort | tumor promoting effect of bmp signaling in endometrial cancer |
| topic | endometrial cancer BMP ACVR1 EMT cancer stem cells |
| url | https://www.mdpi.com/1422-0067/22/15/7882 |
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