Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
MyD88 in DNA repair and cancer cell resistance to genotoxic drugs
Journal of the National Cancer Institute, Volume 105, No. 13, Year 2013
Notification
URL copied to clipboard!
Description
Background MyD88 is an adaptor molecule in Toll-like receptor and interleukin 1 receptor signaling implicated in tumorigenesis through proinflammatory mechanisms. We have recently reported that MyD88 also directly promotes optimal activation of the Ras/Erk pathway. Here we investigate MyD88 implication in the maintenance of the transformation of Ras-dependent tumors. Methods RNA interference was used to inhibit MyD88 expression in the colon cancer cell lines HCT116 and LS513. Apoptosis, DNA damage, p53 function, ERCC1 levels, and Ras and inflammatory signaling pathways were analyzed. Using in vitro assays and xenotransplantation in nude mice (five per group), HCT116 tumor growth was assessed following MyD88 knockdown in presence or absence of chemotherapy. Results MyD88 exerts antiapoptotic functions in colon cancer cells via the Ras/Erk, but not the NF-κB, pathway. MyD88 inhibition leads to defective ERCC1-dependent DNA repair and to accumulation of DNA damage, resulting in cancer cell death via p53. Furthermore, we show that knocking down MyD88 sensitizes cancer cells to genotoxic agents such as platinum salts in vitro and in vivo. Indeed, HCT116 tumor growth following treatment with a combination of suboptimal MyD88 inhibition and suboptimal doses of cisplatin (fold tumor increase = 5.4±1.6) was statistically significantly reduced in comparison to treatment with doxycycline alone (12.4±3.1) or with cisplatin alone (12.5±2.6) (P =. 005 for both, one-sided Student t test). Conclusions Collectively, these results indicate a novel and original link between inflammation, DNA repair, and cancer, and provide further rationale for MyD88 as a potential therapeutic target in Ras-dependent cancers, in the context of concomitant genotoxic chemotherapy. © 2013 © The Author 2013. Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Kfoury, Alain
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Corf, Katy Le
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
El Sabeh, Rana
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Lebanon, Beirut
Université Libanaise
Journeaux, Alexandra
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Badran, Bassam M.
Lebanon, Beirut
Université Libanaise
Hussein, Nader
Lebanon, Beirut
Université Libanaise
Lebecque, Serge
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Manié, Serge
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Renno, Toufic
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Coste, Isabelle
France, Villeurbanne
Université Claude Bernard Lyon 1
France, Lyon
Centre de Recherche en Cancérologie de Lyon
France, Lyon
Le Centre Régional de Lutte Contre le Cancer Léon Bérard
Statistics
Citations: 26
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1093/jnci/djt120
ISSN:
00278874
e-ISSN:
14602105
Research Areas
Cancer
Genetics And Genomics