RT Journal Article
T1 In1-ghrelin splicing variant is associated with reduced disease-free survival of breast cancer patients and increases malignancy of breast cancer cells lines.
A1 Rincon-Fernandez, David
A1 Culler, Michael D
A1 Tsomaia, Natia
A1 Moreno-Bueno, Gema
A1 Luque, Raul M
A1 Gahete, Manuel D
A1 Castaño, Justo P
K1 Ghrelin
K1 Kaplan-Meier estimate
K1 Middle aged
K1 Protein isoforms
AB Ghrelin gene generates several variants that regulate multiple pathophysiological functions, including tumor-related processes. In1-ghrelin is a splicing variant that was previously shown to be overexpressed in breast cancer (BCa), where it correlated with proliferation markers; however, its possible association with clinical outcome of BCa patients and underlying mechanisms are still unknown. To address this issue, expression levels and clinical associations of In1-ghrelin were analyzed in a cohort of 117 BCa samples. Additionally, a battery of cellular and molecular assays was implemented using two BCa cell lines (MCF-7 and MDA-MB-231), wherein the role of In1-ghrelin on proliferation, migration, dedifferentiation and signaling pathways was explored. The results generated revealed that high expression of In1-ghrelin in BCa samples was associated with lymph node metastasis and reduced disease-free survival. Indeed, In1-ghrelin overexpression stimulated proliferation and migration in MCF-7 and MDA-MB-231 cells. Similar results were found by treating MDA-MB-231 and MCF-7 with In1-ghrelin-derived peptides. Conversely, In1-ghrelin silencing decreased proliferation and migration capacities of MDA-MB-231. Furthermore, In1-ghrelin (but not ghrelin) overexpression increased the capacity to form mammospheres in both cell lines. These effects could be associated with activation of MAPK-ERK, Jag1/Notch, Wnt/β-catenin and/or TGF-β1 pathways. Altogether, our data indicate that In1-ghrelin could play relevant functional roles in the regulation of BCa development and progression and may provide insights to identify novel biomarkers and new therapeutic approaches for this pathology.
PB Oxford University Press
YR 2017
FD 2017-12-14
LK http://hdl.handle.net/10668/11942
UL http://hdl.handle.net/10668/11942
LA en
NO Rincón-Fernández D, Culler MD, Tsomaia N, Moreno-Bueno G, Luque RM, Gahete MD, et al. In1-ghrelin splicing variant is associated with reduced disease-free survival of breast cancer patients and increases malignancy of breast cancer cells lines. Carcinogenesis. 2018 Mar 8;39(3):447-457
DS RISalud
RD Apr 14, 2025