@Article{or.2023.042945,
AUTHOR = {JIN-HO CHOI, JOO DONG PARK, SEUNG HEE CHOI, EUN-SU KO, HYE JUNG JANG, KYUNG-SOON PARK},
TITLE = {ELK3-ID4 axis governs the metastatic features of triple negative breast cancer},
JOURNAL = {Oncology Research},
VOLUME = {32},
YEAR = {2024},
NUMBER = {1},
PAGES = {127--138},
URL = {http://www.techscience.com/or/v32n1/54657},
ISSN = {1555-3906},
ABSTRACT = { <b>Purpose:</b> Cancer cell metastasis is a multistep process, and the mechanism underlying extravasation remains unclear. ELK3 is a transcription factor that plays a crucial role in regulating various cellular processes, including cancer metastasis. Based on the finding that ELK3 promotes the metastasis of triple-negative breast cancer (TNBC), we investigated whether ELK3 regulates the extravasation of TNBC by forming the ELK3-ID4 axis. ID4 functions as a transcriptional regulator that interacts with other transcription factors, inhibiting their activity and subsequently influencing various biological processes associated with cell differentiation, survival, growth, and metastasis. <b>Methods:</b> We assessed the correlation between the expression of ELK3 and that of ID4 in TNBCs using bioinformatics analyses, QRT-PCR, western blot analysis, luciferase reporter assays, and chromatin immunoprecipitation. Migration, adhesion, invasion, and lung metastasis assays were employed to determine whether the ELK3-ID4 axis regulates the metastatic features of TNBC. <b>Results:</b> We found that ELK3 binds directly to a binding motif close to the ID4 promoter to repress promoter activity. The expression of E-cadherin in TNBC was regulated by the ELK3-ID4 axis. <i>In vitro</i> and <i>in vivo</i> analyses showed that inhibiting ID4 expression in ELK3-knockdown MDA-MB-231 (ELK3KD) cells restored the ability to extravasate and metastasize. <b>Conclusion:</b> The results indicate that the ELK3 regulates ID4 promoter activity, and that the ELK3-ID4 axis regulates the metastatic characteristics of TNBC cells. Additionally, the data suggest that the ELK3-ID4 axis regulates metastasis of TNBCs by modulating expression of E-cadherin.},
DOI = {10.32604/or.2023.042945}
}