A5030300970- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Protein Degradation and Inhibitors
- Melanoma and MAPK Pathways
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- RNA regulation and disease
- RNA Research and Splicing
VIB-KU Leuven Center for Cancer Biology
2020-2024
KU Leuven
2021
The ability to adapt environmental stress, including therapeutic insult, contributes tumor evolution and drug resistance. In suboptimal conditions, the integrated stress response (ISR) promotes survival by dampening cytosolic translation. We show that ISR-dependent also relies on a concomitant up-regulation of mitochondrial protein synthesis, vulnerability can be exploited using mitoribosome-targeting antibiotics. Accordingly, such agents sensitized MAPK inhibition, thus preventing...
Abstract Although immune checkpoint blockade (ICB) has revolutionized cancer treatment, resistance mechanisms limit its clinical benefit. Here we characterise LISRR , a cancer-specific lncRNA highly expressed in melanoma patients refractory to ICB. In cells undergoing (therapeutic) stress, recruits DAZAP1 (Deleted AZoospermia Associated Protein 1) polysomes and drives the assembly of subset ribosomes at endoplasmic reticulum, directing synthesis an immunosuppressive translatome. This...
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Summary Therapy resistance remains a major clinical challenge for the management of metastatic melanoma. Here we show that activation Integrated Stress Response (ISR), which is common in drug-tolerant and resistant melanoma, promotes selective synthesis mitochondrial proteins cytosol. Since translation adapts to influx nuclear-encoded proteins, ISR indirectly enhances makes these cells highly vulnerable inhibitors. Treatment melanoma with mitoribosome-targeting antibiotics, induces...