Humanin Promotes Tumor Progression in Experimental Triple Negative Breast Cancer.
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Apoptosis
Biomarkers, Tumor
/ genetics
Cell Proliferation
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Lung Neoplasms
/ metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Prognosis
Survival Rate
Triple Negative Breast Neoplasms
/ metabolism
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 05 2020
22 05 2020
Historique:
received:
30
05
2019
accepted:
29
04
2020
entrez:
24
5
2020
pubmed:
24
5
2020
medline:
2
12
2020
Statut:
epublish
Résumé
Humanin (HN) is a mitochondrial-derived peptide with cytoprotective effect in many tissues. Administration of HN analogs has been proposed as therapeutic approach for degenerative diseases. Although HN has been shown to protect normal tissues from chemotherapy, its role in tumor pathogenesis is poorly understood. Here, we evaluated the effect of HN on the progression of experimental triple negative breast cancer (TNBC). The meta-analysis of transcriptomic data from The Cancer Genome Atlas indicated that HN and its receptors are expressed in breast cancer specimens. By immunohistochemistry we observed up-regulation of HN in TNBC biopsies when compared to mammary gland sections from healthy donors. Addition of exogenous HN protected TNBC cells from apoptotic stimuli whereas shRNA-mediated HN silencing reduced their viability and enhanced their chemo-sensitivity. Systemic administration of HN in TNBC-bearing mice reduced tumor apoptotic rate, impaired the antitumor and anti-metastatic effect of chemotherapy and stimulated tumor progression, accelerating tumor growth and development of spontaneous lung metastases. These findings suggest that HN may exert pro-tumoral effects and thus, caution should be taken when using exogenous HN to treat degenerative diseases. In addition, our study suggests that HN blockade could constitute a therapeutic strategy to improve the efficacy of chemotherapy in breast cancer.
Identifiants
pubmed: 32444831
doi: 10.1038/s41598-020-65381-7
pii: 10.1038/s41598-020-65381-7
pmc: PMC7244539
doi:
Substances chimiques
Biomarkers, Tumor
0
Intracellular Signaling Peptides and Proteins
0
humanin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8542Références
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