A5017648269- Chromatin Remodeling and Cancer
- Immune Cell Function and Interaction
- Protein Degradation and Inhibitors
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- RNA regulation and disease
- RNA Research and Splicing
- Cancer therapeutics and mechanisms
- NF-κB Signaling Pathways
- Cancer Research and Treatments
- Melanoma and MAPK Pathways
- Hippo pathway signaling and YAP/TAZ
- Cancer-related Molecular Pathways
- Helicobacter pylori-related gastroenterology studies
- Renal and related cancers
- Cancer Mechanisms and Therapy
- Cutaneous Melanoma Detection and Management
- interferon and immune responses
- Signaling Pathways in Disease
- DNA Repair Mechanisms
Centro de Investigación Biomédica en Red de Cáncer
2019-2025
Hospital Del Mar
2025
Hospital del Mar Research Institute
2019-2023
Universitat Autònoma de Barcelona
2023
The DNA damage repair kinase ATM is phosphorylated by the NF-κB pathway IKKα, resulting in enhanced through nonhomologous end-joining pathway. Thus, inhibition of IKKα enhances efficacy cancer therapy based on inducing damage. Here, we found a role for IKK regulatory subunit NEMO mediated and IKKα. Exposure to damaging agents induced interaction with preformed ATM-IKKα complex, which was required target active chromatin efficient but not activating ATM. Recognition damaged IKKα-NEMO-ATM...
Phosphorylated IKKα(p45) is a nuclear active form of the IKKα kinase that induced by MAP kinases BRAF and TAK1 promotes tumor growth independent canonical NF-κB signaling. Insights into sources activation its downstream substrates in nucleus remain to be defined. Here, we discover rapidly activated DNA damage ATM-ATR, but dependent on BRAF-TAK1-p38-MAPK, required for robust ATM efficient repair. Abolishing or activity attenuates ATM, Chk1, MDC1, Kap1, 53BP1 phosphorylation, compromises RIF1...
Abstract Current therapy against colorectal cancer (CRC) is based on DNA-damaging agents that remain ineffective in a proportion of patients. Whether and how non-curative DNA damage-based treatment affects tumor cell behavior patient outcome primarily unstudied. Using CRC patient-derived organoids (PDO)s, we show sublethal doses chemotherapy (CT) does not select previously resistant populations but induces quiescent state specifically to TP53 wildtype (WT) cells, which linked the acquisition...
Fifteen percent of colorectal cancer (CRC) cells exhibit a mucin hypersecretory phenotype, which is suggested to provide resistance immune surveillance and chemotherapy. We now formally show that CRC build barrier chemotherapeutics by increasing mucins’ secretion. low levels KChIP3, negative regulator secretion (Cantero-Recasens et al., 2018), risk factor for patients’ relapse in subset untreated tumours. Our results also reveal depleted KChIP3 are four times more resistant (measured as cell...
ABSTRACT Alternative splicing allows multiple transcripts to be generated from the same gene diversify protein repertoire and gain new functions despite a limited coding genome. It can impact wide spectrum of biological processes, including disease. However, its significance has long been underestimated due limitations in dissecting precise role each isoform physiological context. Furthermore, identifying key regulatory elements correct deleterious isoforms proven equally challenging,...
Abstract Alternative splicing allows multiple transcripts to be generated from the same gene diversify protein repertoire and gain new functions despite a limited coding genome. It can impact wide spectrum of biological processes, including disease. However, its significance has long been underestimated due limitations in dissecting precise role each isoform physiological context. Furthermore, identifying key regulatory elements correct deleterious isoforms proven equally challenging,...
Abstract Activation of the IKK kinase complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification downstream effectors other than NF-kB remained elusive. Analysis IKK-dependent substrates after UV-treatment revealed that BRD4 phosphorylation by IKKa is required for chromatin-binding dynamics upon damage. Moreover, induces NF-kB-dependent transcription LIF leading STAT3 activation, association recruitment specific target genes. abrogation...
SUMMARY Activation of the IKK kinase complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification downstream effectors other than NF-κB remained elusive. Analysis IKK-dependent substrates after UV-treatment revealed that BRD4 phosphorylation by IKKα is required for chromatin-binding dynamics upon damage. Moreover, induces NF-κB-dependent transcription LIF leading STAT3 activation, association recruitment specific target genes. abrogation...
We previously demonstrated that IKKα binds and phosphorylates ATM, thereby enhancing DNA damage repair by the non-homologous end joining pathway. Thus, inhibition of enhances efficacy damage-based cancer therapy. have now dissected elements downstream IKKa participate in this resistance mechanism. here demonstrate NEMO physically interacts with a preformed ATM-IKKα complex after exposure to damaging agents. is dispensable for ATM activation DDR signaling, but required drive active chromatin...
Abstract Activation of the IKK kinase complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification downstream effectors other than NF-kB remained elusive. Analysis IKK-dependent substrates after UV-treatment revealed that BRD4 phosphorylation by IKKa is required for chromatin-binding dynamics upon damage. Moreover, induces NF-kB-dependent transcription LIF leading STAT3 activation, association recruitment specific target genes. abrogation...
ABSTRACT 15% of colorectal cancers (CRC) cells exhibit a mucin hypersecretory phenotype, which is suggested to provide resistance immune surveillance and chemotherapy. We now formally show that cancer build barrier chemotherapeutics by increasing mucins’ secretion. low levels KChIP3, negative regulator secretion (Cantero-Recasens et al ., 2018), risk factor for CRC patients’ relapse in subset untreated tumours. Our results also reveal depleted KChIP3 are four times more resistant (measured...