| Autor: |
Estefania Cuesta-Borràs, Cándida Salvans, Oriol Arqués, Irene Chicote, Lorena Ramírez, Laia Cabellos, Jordi Martínez-Quintanilla, Alex Mur-Espinosa, Alejandro García-Álvarez, Jorge Hernando, Juan Ramón Tejedor, Oriol Mirallas, Elena Élez, Mario F. Fraga, Josep Tabernero, Paolo Nuciforo, Jaume Capdevila, Héctor G. Palmer, Isabel Puig |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 42, Iss 8, Pp 112927- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2023.112927 |
| Popis: |
Summary: Tumor relapse is linked to rapid chemoresistance and represents a bottleneck for cancer therapy success. Engagement of a reduced proliferation state is a non-mutational mechanism exploited by cancer cells to bypass therapy-induced cell death. Through combining functional pulse-chase experiments in engineered cells and transcriptomic analyses, we identify DPPA3 as a master regulator of slow-cycling and chemoresistant phenotype in colorectal cancer (CRC). We find a vicious DPPA3-HIF1α feedback loop that downregulates FOXM1 expression via DNA methylation, thereby delaying cell-cycle progression. Moreover, downregulation of HIF1α partially restores a chemosensitive proliferative phenotype in DPPA3-overexpressing cancer cells. In cohorts of CRC patient samples, DPPA3 overexpression acts as a predictive biomarker of chemotherapeutic resistance that subsequently requires reduction in its expression to allow metastatic outgrowth. Our work demonstrates that slow-cycling cancer cells exploit a DPPA3/HIF1α axis to support tumor persistence under therapeutic stress and provides insights on the molecular regulation of disease progression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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