Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression
- Authors
- Oh, Se Jin; Noh, Kyung Hee; Song, Kwon-Ho; Kim, Tae Woo
- Issue Date
- 8월-2021
- Publisher
- MDPI
- Keywords
- AKT; Jun activation domain-binding protein 1 (JAB1); cancer; cancer stem cell (CSC); chemo-resistance; epidermal growth factor (EGF); epidermal growth factor receptor (EGFR); immune resistance; synaptonemal complex protein 3 (SCP3)
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.22, no.16
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 22
- Number
- 16
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/137029
- DOI
- 10.3390/ijms22168839
- ISSN
- 1661-6596
- Abstract
- 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(high) therapeutic-refractory cancer.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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