Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression
Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, has been implicated in cancer progression, and therapeutic resistance, as well as cancer stem cell (CSC)-like properties. Previously, we demonstrated that SCP3 promotes these aggressive phenotypes via hyperactivation of the AKT sign...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8839 |
| _version_ | 1797523561678635008 |
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| author | Se Jin Oh Kyung Hee Noh Kwon-Ho Song Tae Woo Kim |
| author_facet | Se Jin Oh Kyung Hee Noh Kwon-Ho Song Tae Woo Kim |
| author_sort | Se Jin Oh |
| collection | DOAJ |
| description | Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, has been implicated in cancer progression, and therapeutic resistance, as well as cancer stem cell (CSC)-like properties. Previously, we demonstrated that SCP3 promotes these aggressive phenotypes via hyperactivation of the AKT signaling pathway; however, the underlying mechanisms responsible for SCP3-induced AKT activation remain to be elucidated. In this study, we demonstrated that the EGF-EGFR axis is the primary route through which SCP3 acts to activate AKT signaling. SCP3 triggers the EGFR-AKT pathway through transcriptional activation of EGF. Notably, neutralization of secreted EGF by its specific monoclonal antibody reversed SCP3-mediated aggressive phenotypes with a concomitant reversal of EGFR-AKT activation. In an effort to elucidate the molecular mechanisms underlying SCP3-induced transcriptional activation of EGF, we identified Jun activation domain-binding protein 1 (JAB1) as a binding partner of SCP3 using a yeast two-hybrid (Y2H) assay system, and we demonstrated that SCP3 induces EGF transcription through physical interaction with JAB1. Thus, our findings establish a firm molecular link among SCP3, EGFR, and AKT by identifying the novel roles of SCP3 in transcriptional regulation. We believe that these findings hold important implications for controlling SCP3<sup>high</sup> therapeutic-refractory cancer. |
| first_indexed | 2024-03-10T08:43:48Z |
| format | Article |
| id | doaj.art-51f7070e970b4c9099a1912b1d2a37aa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:43:48Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-51f7070e970b4c9099a1912b1d2a37aa2023-11-22T08:01:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216883910.3390/ijms22168839Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF ExpressionSe Jin Oh0Kyung Hee Noh1Kwon-Ho Song2Tae Woo Kim3BK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, KoreaGene Therapy Research Unit, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, KoreaDepartment of Cell Biology, Daegu Catholic University School of Medicine, Daegu 42472, KoreaBK21 Graduate Program, Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, KoreaSynaptonemal complex protein 3 (SCP3), a member of the Cor1 family, has been implicated in cancer progression, and therapeutic resistance, as well as cancer stem cell (CSC)-like properties. Previously, we demonstrated that SCP3 promotes these aggressive phenotypes via hyperactivation of the AKT signaling pathway; however, the underlying mechanisms responsible for SCP3-induced AKT activation remain to be elucidated. In this study, we demonstrated that the EGF-EGFR axis is the primary route through which SCP3 acts to activate AKT signaling. SCP3 triggers the EGFR-AKT pathway through transcriptional activation of EGF. Notably, neutralization of secreted EGF by its specific monoclonal antibody reversed SCP3-mediated aggressive phenotypes with a concomitant reversal of EGFR-AKT activation. In an effort to elucidate the molecular mechanisms underlying SCP3-induced transcriptional activation of EGF, we identified Jun activation domain-binding protein 1 (JAB1) as a binding partner of SCP3 using a yeast two-hybrid (Y2H) assay system, and we demonstrated that SCP3 induces EGF transcription through physical interaction with JAB1. Thus, our findings establish a firm molecular link among SCP3, EGFR, and AKT by identifying the novel roles of SCP3 in transcriptional regulation. We believe that these findings hold important implications for controlling SCP3<sup>high</sup> therapeutic-refractory cancer.https://www.mdpi.com/1422-0067/22/16/8839synaptonemal complex protein 3 (SCP3)Jun activation domain-binding protein 1 (JAB1)epidermal growth factor (EGF)epidermal growth factor receptor (EGFR)AKTcancer |
| spellingShingle | Se Jin Oh Kyung Hee Noh Kwon-Ho Song Tae Woo Kim Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression International Journal of Molecular Sciences synaptonemal complex protein 3 (SCP3) Jun activation domain-binding protein 1 (JAB1) epidermal growth factor (EGF) epidermal growth factor receptor (EGFR) AKT cancer |
| title | Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression |
| title_full | Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression |
| title_fullStr | Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression |
| title_full_unstemmed | Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression |
| title_short | Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression |
| title_sort | interaction between scp3 and jab1 confers cancer therapeutic resistance and stem like properties through egf expression |
| topic | synaptonemal complex protein 3 (SCP3) Jun activation domain-binding protein 1 (JAB1) epidermal growth factor (EGF) epidermal growth factor receptor (EGFR) AKT cancer |
| url | https://www.mdpi.com/1422-0067/22/16/8839 |
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