Cargando…
ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation
Lung cancer is the most lethal malignancies with high aggressive and poor prognosis. Until now, the five-year survival rate has not been improved which brings serious challenge to human health. Lung cancer stem cells (LCSCs) serve as the root of cancer occurrence, progression, recurrence, and drug r...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060425/ https://www.ncbi.nlm.nih.gov/pubmed/36990974 http://dx.doi.org/10.1038/s41389-023-00462-6 |
Sumario: | Lung cancer is the most lethal malignancies with high aggressive and poor prognosis. Until now, the five-year survival rate has not been improved which brings serious challenge to human health. Lung cancer stem cells (LCSCs) serve as the root of cancer occurrence, progression, recurrence, and drug resistance. Therefore, effective anti-cancer agents and molecular mechanisms which could specifically eliminate LCSCs are urgently needed for drug design. In this article, we discovered Olig2 was overexpressed in clinical lung cancer tissues and acted as a transcription factor to regulate cancer stemness by regulating CD133 gene transcription. The results suggested Olig2 could be a promising target in anti-LCSCs therapy and new drugs targeted Olig2 may exhibit excellent clinical results. Furthermore, we verified ACT001, a guaianolide sesquiterpene lactone in phase II clinical trial with excellent glioma remission, inhibited cancer stemness by directly binding to Olig2 protein, inducing Olig2 ubiquitination degradation and inhibiting CD133 gene transcription. All these results suggested that Olig2 could be an excellent druggable target in anti-LCSCs therapy and lay a foundation for the further application of ACT001 in the treatment of lung cancer in clinical. |
---|