TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer Cells
We have previously observed that tropomyosin receptor kinase B (TrkB) induces breast cancer metastasis by activating both the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and phosphatidylinositol-3-Kinase (PI3K)/AKT signaling pathways and inhibiting runt-related tra...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/8/2095 |
| _version_ | 1797561092855037952 |
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| author | Min Soo Kim Wook Jin |
| author_facet | Min Soo Kim Wook Jin |
| author_sort | Min Soo Kim |
| collection | DOAJ |
| description | We have previously observed that tropomyosin receptor kinase B (TrkB) induces breast cancer metastasis by activating both the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and phosphatidylinositol-3-Kinase (PI3K)/AKT signaling pathways and inhibiting runt-related transcription factor 3 (RUNX3) and kelch-like ECH-associated protein 1 (KEAP1). These studies indicated that TrkB expression is crucial to the pathogenesis of breast cancer. However, how TrkB regulates bone morphogenetic protein (BMP) signaling and tumor suppression is largely unknown. Herein, we report that TrkB is a key regulator of BMP-mediated tumor suppression. TrkB enhances the metastatic potential of cancer cells by promoting cell anchorage-independent growth, migration, and suppressing BMP-2-mediated growth inhibition. TrkB inhibits the BMP-mediated activation of SMAD family member 1 (SMAD1) by promoting the formation of the TrkB/BMP type II receptor complex and suppresses RUNX3 by depleting BMP receptor I (BMPRI) expression. In addition, the knockdown of TrkB restored the tumor-inhibitory effect of BMP-2 via the activation of SMAD1. Moreover, the TrkB kinase activity was required for its effect on BMP signaling. Our study identified a unique role of TrkB in the regulation of BMP-mediated growth inhibition and BMP-2-induced RUNX3 expression. |
| first_indexed | 2024-03-10T18:09:24Z |
| format | Article |
| id | doaj.art-b239e590bb104b3dbe6df65ce7bba20b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:09:24Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b239e590bb104b3dbe6df65ce7bba20b2023-11-20T08:13:48ZengMDPI AGCancers2072-66942020-07-01128209510.3390/cancers12082095TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer CellsMin Soo Kim0Wook Jin1Laboratory of Molecular Disease and Cell Regulation, Department of Biochemistry, School of Medicine, Gachon University, Incheon 21999, KoreaLaboratory of Molecular Disease and Cell Regulation, Department of Biochemistry, School of Medicine, Gachon University, Incheon 21999, KoreaWe have previously observed that tropomyosin receptor kinase B (TrkB) induces breast cancer metastasis by activating both the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and phosphatidylinositol-3-Kinase (PI3K)/AKT signaling pathways and inhibiting runt-related transcription factor 3 (RUNX3) and kelch-like ECH-associated protein 1 (KEAP1). These studies indicated that TrkB expression is crucial to the pathogenesis of breast cancer. However, how TrkB regulates bone morphogenetic protein (BMP) signaling and tumor suppression is largely unknown. Herein, we report that TrkB is a key regulator of BMP-mediated tumor suppression. TrkB enhances the metastatic potential of cancer cells by promoting cell anchorage-independent growth, migration, and suppressing BMP-2-mediated growth inhibition. TrkB inhibits the BMP-mediated activation of SMAD family member 1 (SMAD1) by promoting the formation of the TrkB/BMP type II receptor complex and suppresses RUNX3 by depleting BMP receptor I (BMPRI) expression. In addition, the knockdown of TrkB restored the tumor-inhibitory effect of BMP-2 via the activation of SMAD1. Moreover, the TrkB kinase activity was required for its effect on BMP signaling. Our study identified a unique role of TrkB in the regulation of BMP-mediated growth inhibition and BMP-2-induced RUNX3 expression.https://www.mdpi.com/2072-6694/12/8/2095TrkBbone morphogenetic proteins (BMPs)BMP type I (BMPRI) and BMP type II (BMPRII) receptortumor suppressor activitytumor progression |
| spellingShingle | Min Soo Kim Wook Jin TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer Cells Cancers TrkB bone morphogenetic proteins (BMPs) BMP type I (BMPRI) and BMP type II (BMPRII) receptor tumor suppressor activity tumor progression |
| title | TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer Cells |
| title_full | TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer Cells |
| title_fullStr | TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer Cells |
| title_full_unstemmed | TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer Cells |
| title_short | TrkB Inhibits the BMP Signaling-Mediated Growth Inhibition of Cancer Cells |
| title_sort | trkb inhibits the bmp signaling mediated growth inhibition of cancer cells |
| topic | TrkB bone morphogenetic proteins (BMPs) BMP type I (BMPRI) and BMP type II (BMPRII) receptor tumor suppressor activity tumor progression |
| url | https://www.mdpi.com/2072-6694/12/8/2095 |
| work_keys_str_mv | AT minsookim trkbinhibitsthebmpsignalingmediatedgrowthinhibitionofcancercells AT wookjin trkbinhibitsthebmpsignalingmediatedgrowthinhibitionofcancercells |