| Title |
Pro-apoptotic signaling induced by Retinoic acid and dsRNA is under the control of Interferon Regulatory Factor-3 in breast cancer cells
|
|---|---|
| Published in |
Apoptosis, April 2017
|
| DOI | 10.1007/s10495-017-1377-z |
| Pubmed ID | |
| Authors |
Ana R. Bernardo, José M. Cosgaya, Ana Aranda, Ana M. Jiménez-Lara |
| Abstract |
Breast cancer is one of the most lethal malignancies for women. Retinoic acid (RA) and double-stranded RNA (dsRNA) are considered signaling molecules with potential anticancer activity. RA, co-administered with the dsRNA mimic polyinosinic-polycytidylic acid (poly(I:C)), synergizes to induce a TRAIL (Tumor-Necrosis-Factor Related Apoptosis-Inducing Ligand)- dependent apoptotic program in breast cancer cells. Here, we report that RA/poly(I:C) co-treatment, synergically, induce the activation of Interferon Regulatory Factor-3 (IRF3) in breast cancer cells. IRF3 activation is mediated by a member of the pathogen recognition receptors, Toll-like receptor-3 (TLR3), since its depletion abrogates IRF3 activation by RA/poly(I:C) co-treatment. Besides induction of TRAIL, apoptosis induced by RA/poly(I:C) correlates with the increased expression of pro-apoptotic TRAIL receptors, TRAIL-R1/2, and the inhibition of the antagonistic receptors TRAIL-R3/4. IRF3 plays an important role in RA/poly(I:C)-induced apoptosis since IRF3 depletion suppresses caspase-8 and caspase-3 activation, TRAIL expression upregulation and apoptosis. Interestingly, RA/poly(I:C) combination synergizes to induce a bioactive autocrine/paracrine loop of type-I Interferons (IFNs) which is ultimately responsible for TRAIL and TRAIL-R1/2 expression upregulation, while inhibition of TRAIL-R3/4 expression is type-I IFN-independent. Our results highlight the importance of IRF3 and type-I IFNs signaling for the pro-apoptotic effects induced by RA and synthetic dsRNA in breast cancer cells. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 12 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 2 | 17% |
| Student > Ph. D. Student | 2 | 17% |
| Student > Bachelor | 1 | 8% |
| Researcher | 1 | 8% |
| Student > Doctoral Student | 1 | 8% |
| Other | 1 | 8% |
| Unknown | 4 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 25% |
| Medicine and Dentistry | 2 | 17% |
| Chemical Engineering | 1 | 8% |
| Neuroscience | 1 | 8% |
| Agricultural and Biological Sciences | 1 | 8% |
| Other | 0 | 0% |
| Unknown | 4 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 April 2017.
All research outputs
#20,413,129
of 22,963,381 outputs
Outputs from Apoptosis
#634
of 809 outputs
Outputs of similar age
#270,123
of 310,038 outputs
Outputs of similar age from Apoptosis
#7
of 12 outputs
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