RHOA < sup > L57V < /sup > drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling
Sci Signal. 2023 Dec 19;16(816):eadg5289. doi: 10.1126/scisignal.adg5289. Epub 2023 Dec 19.ABSTRACTCancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr42-to-Cys (Y42C) and Leu57-to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1, which encodes the cell ad...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Antje Schaefer Richard G Hodge Haisheng Zhang G Aaron Hobbs Julien Dilly Minh V Huynh Craig M Goodwin Feifei Zhang J Nathaniel Diehl Mariaelena Pierobon Elisa Baldelli Sehrish Javaid Karson Guthrie Naim U Rashid Emanuel F Petricoin Adrienne D Cox William Source Type: research
RHOA drivers take alternate routes in gastric cancer
Sci Signal. 2023 Dec 19;16(816):eadk9171. doi: 10.1126/scisignal.adk9171. Epub 2023 Dec 19.ABSTRACTOncogenic small guanosine triphosphatases (GTPases) are often characterized by a limited set of activating mutations that affect their intrinsic biochemical function, but RHOA-which is frequently mutated in gastric cancer-appears not to have read the instruction manual. Having previously characterized the Y42C RHOA mutation in gastric cancer, in this issue of Science Signaling, Schaefer et al. take on the slightly less common L57V mutation and find that individual RHOA mutations can have different and unpredictable signaling ...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Dorothy Benton Jonathan Chernoff Source Type: research
A noncanonical IRAK4-IRAK1 pathway counters DNA damage-induced apoptosis independently of TLR/IL-1R signaling
Sci Signal. 2023 Dec 19;16(816):eadh3449. doi: 10.1126/scisignal.adh3449. Epub 2023 Dec 19.ABSTRACTInterleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptors (TLRs) and IL-1R in innate immunity. Here, we found that IRAK4 and IRAK1 together inhibited DNA damage-induced cell death independently of TLR or IL-1R signaling. In human cancer cells, IRAK4 was activated downstream of ATR kinase in response to double-strand breaks (DSBs) induced by ionizing radiation (IR). Activated IRAK4 then formed a complex with and activated IRAK1. The formation of this complex required the E3 ubiquitin l...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Yuanyuan Li Richa B Shah Samanta Sarti Alicia L Belcher Brian J Lee Andrej Gorbatenko Francesca Nemati Honglin Yu Zoe Stanley Mahbuba Rahman Zhengping Shao Jose M Silva Shan Zha Samuel Sidi Source Type: research
TB impairs DNA repair
Sci Signal. 2023 Dec 19;16(816):eadn5031. doi: 10.1126/scisignal.adn5031. Epub 2023 Dec 19.ABSTRACTA Mycobacterium tuberculosis virulence factor promotes foam cell formation by inhibiting DNA repair.PMID:38113336 | DOI:10.1126/scisignal.adn5031 (Source: Science Signaling)
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Annalisa M VanHook Source Type: research
Inhibition of the lysine demethylase LSD1 modulates the balance between inflammatory and antiviral responses against coronaviruses
Sci Signal. 2023 Dec 19;16(816):eade0326. doi: 10.1126/scisignal.ade0326. Epub 2023 Dec 19.ABSTRACTInnate immune responses to coronavirus infections are highly cell specific. Tissue-resident macrophages, which are infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients but are inconsistently infected in vitro, exert critical but conflicting effects by secreting both antiviral type I interferons (IFNs) and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for the treatment of coronavirus disease 2019 (COVID-19), indiscriminately suppress both respo...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Luca Mazzarella Fabio Santoro Roberto Ravasio Valeria Fumagalli Paul E Massa Simona Rodighiero Elena Gavil án Mauro Romanenghi Bruno A Duso Emanuele Bonetti Lara Manganaro Rani Pallavi Deborah Trastulli Isabella Pallavicini Claudia Gentile Silvia Monzani Source Type: research
RHOA < sup > L57V < /sup > drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling
Sci Signal. 2023 Dec 19;16(816):eadg5289. doi: 10.1126/scisignal.adg5289. Epub 2023 Dec 19.ABSTRACTCancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr42-to-Cys (Y42C) and Leu57-to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1, which encodes the cell ad...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Antje Schaefer Richard G Hodge Haisheng Zhang G Aaron Hobbs Julien Dilly Minh V Huynh Craig M Goodwin Feifei Zhang J Nathaniel Diehl Mariaelena Pierobon Elisa Baldelli Sehrish Javaid Karson Guthrie Naim U Rashid Emanuel F Petricoin Adrienne D Cox William Source Type: research
RHOA drivers take alternate routes in gastric cancer
Sci Signal. 2023 Dec 19;16(816):eadk9171. doi: 10.1126/scisignal.adk9171. Epub 2023 Dec 19.ABSTRACTOncogenic small guanosine triphosphatases (GTPases) are often characterized by a limited set of activating mutations that affect their intrinsic biochemical function, but RHOA-which is frequently mutated in gastric cancer-appears not to have read the instruction manual. Having previously characterized the Y42C RHOA mutation in gastric cancer, in this issue of Science Signaling, Schaefer et al. take on the slightly less common L57V mutation and find that individual RHOA mutations can have different and unpredictable signaling ...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Dorothy Benton Jonathan Chernoff Source Type: research
A noncanonical IRAK4-IRAK1 pathway counters DNA damage-induced apoptosis independently of TLR/IL-1R signaling
Sci Signal. 2023 Dec 19;16(816):eadh3449. doi: 10.1126/scisignal.adh3449. Epub 2023 Dec 19.ABSTRACTInterleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptors (TLRs) and IL-1R in innate immunity. Here, we found that IRAK4 and IRAK1 together inhibited DNA damage-induced cell death independently of TLR or IL-1R signaling. In human cancer cells, IRAK4 was activated downstream of ATR kinase in response to double-strand breaks (DSBs) induced by ionizing radiation (IR). Activated IRAK4 then formed a complex with and activated IRAK1. The formation of this complex required the E3 ubiquitin l...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Yuanyuan Li Richa B Shah Samanta Sarti Alicia L Belcher Brian J Lee Andrej Gorbatenko Francesca Nemati Honglin Yu Zoe Stanley Mahbuba Rahman Zhengping Shao Jose M Silva Shan Zha Samuel Sidi Source Type: research
TB impairs DNA repair
Sci Signal. 2023 Dec 19;16(816):eadn5031. doi: 10.1126/scisignal.adn5031. Epub 2023 Dec 19.ABSTRACTA Mycobacterium tuberculosis virulence factor promotes foam cell formation by inhibiting DNA repair.PMID:38113336 | DOI:10.1126/scisignal.adn5031 (Source: Science Signaling)
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Annalisa M VanHook Source Type: research
Inhibition of the lysine demethylase LSD1 modulates the balance between inflammatory and antiviral responses against coronaviruses
Sci Signal. 2023 Dec 19;16(816):eade0326. doi: 10.1126/scisignal.ade0326. Epub 2023 Dec 19.ABSTRACTInnate immune responses to coronavirus infections are highly cell specific. Tissue-resident macrophages, which are infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients but are inconsistently infected in vitro, exert critical but conflicting effects by secreting both antiviral type I interferons (IFNs) and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for the treatment of coronavirus disease 2019 (COVID-19), indiscriminately suppress both respo...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Luca Mazzarella Fabio Santoro Roberto Ravasio Valeria Fumagalli Paul E Massa Simona Rodighiero Elena Gavil án Mauro Romanenghi Bruno A Duso Emanuele Bonetti Lara Manganaro Rani Pallavi Deborah Trastulli Isabella Pallavicini Claudia Gentile Silvia Monzani Source Type: research
RHOA < sup > L57V < /sup > drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling
Sci Signal. 2023 Dec 19;16(816):eadg5289. doi: 10.1126/scisignal.adg5289. Epub 2023 Dec 19.ABSTRACTCancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr42-to-Cys (Y42C) and Leu57-to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1, which encodes the cell ad...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Antje Schaefer Richard G Hodge Haisheng Zhang G Aaron Hobbs Julien Dilly Minh V Huynh Craig M Goodwin Feifei Zhang J Nathaniel Diehl Mariaelena Pierobon Elisa Baldelli Sehrish Javaid Karson Guthrie Naim U Rashid Emanuel F Petricoin Adrienne D Cox William Source Type: research
RHOA drivers take alternate routes in gastric cancer
Sci Signal. 2023 Dec 19;16(816):eadk9171. doi: 10.1126/scisignal.adk9171. Epub 2023 Dec 19.ABSTRACTOncogenic small guanosine triphosphatases (GTPases) are often characterized by a limited set of activating mutations that affect their intrinsic biochemical function, but RHOA-which is frequently mutated in gastric cancer-appears not to have read the instruction manual. Having previously characterized the Y42C RHOA mutation in gastric cancer, in this issue of Science Signaling, Schaefer et al. take on the slightly less common L57V mutation and find that individual RHOA mutations can have different and unpredictable signaling ...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Dorothy Benton Jonathan Chernoff Source Type: research
A noncanonical IRAK4-IRAK1 pathway counters DNA damage-induced apoptosis independently of TLR/IL-1R signaling
Sci Signal. 2023 Dec 19;16(816):eadh3449. doi: 10.1126/scisignal.adh3449. Epub 2023 Dec 19.ABSTRACTInterleukin-1 receptor (IL-1R)-associated kinases (IRAKs) are core effectors of Toll-like receptors (TLRs) and IL-1R in innate immunity. Here, we found that IRAK4 and IRAK1 together inhibited DNA damage-induced cell death independently of TLR or IL-1R signaling. In human cancer cells, IRAK4 was activated downstream of ATR kinase in response to double-strand breaks (DSBs) induced by ionizing radiation (IR). Activated IRAK4 then formed a complex with and activated IRAK1. The formation of this complex required the E3 ubiquitin l...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Yuanyuan Li Richa B Shah Samanta Sarti Alicia L Belcher Brian J Lee Andrej Gorbatenko Francesca Nemati Honglin Yu Zoe Stanley Mahbuba Rahman Zhengping Shao Jose M Silva Shan Zha Samuel Sidi Source Type: research
TB impairs DNA repair
Sci Signal. 2023 Dec 19;16(816):eadn5031. doi: 10.1126/scisignal.adn5031. Epub 2023 Dec 19.ABSTRACTA Mycobacterium tuberculosis virulence factor promotes foam cell formation by inhibiting DNA repair.PMID:38113336 | DOI:10.1126/scisignal.adn5031 (Source: Science Signaling)
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Annalisa M VanHook Source Type: research
Inhibition of the lysine demethylase LSD1 modulates the balance between inflammatory and antiviral responses against coronaviruses
Sci Signal. 2023 Dec 19;16(816):eade0326. doi: 10.1126/scisignal.ade0326. Epub 2023 Dec 19.ABSTRACTInnate immune responses to coronavirus infections are highly cell specific. Tissue-resident macrophages, which are infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients but are inconsistently infected in vitro, exert critical but conflicting effects by secreting both antiviral type I interferons (IFNs) and tissue-damaging inflammatory cytokines. Steroids, the only class of host-targeting drugs approved for the treatment of coronavirus disease 2019 (COVID-19), indiscriminately suppress both respo...
Source: Science Signaling - December 19, 2023 Category: Biomedical Science Authors: Luca Mazzarella Fabio Santoro Roberto Ravasio Valeria Fumagalli Paul E Massa Simona Rodighiero Elena Gavil án Mauro Romanenghi Bruno A Duso Emanuele Bonetti Lara Manganaro Rani Pallavi Deborah Trastulli Isabella Pallavicini Claudia Gentile Silvia Monzani Source Type: research
