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Circulating levels of MOTS-c in patients with breast cancer treated with metformin
The mitokine MOTS-c is a mitochondrially-encoded “exercise-mimetic peptide” expressed in multiple tissues, particularly skeletal muscles, which can be detected as a circulating hormone in the blood. MOTS-c mechanisms of action (MoA) involve insulin sensitization, enhanced glucose utilization, suppre...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10008497/ https://www.ncbi.nlm.nih.gov/pubmed/36490309 http://dx.doi.org/10.18632/aging.204423 |
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author | Cuyàs, Elisabet Verdura, Sara Martin-Castillo, Begoña Menendez, Javier A. |
author_facet | Cuyàs, Elisabet Verdura, Sara Martin-Castillo, Begoña Menendez, Javier A. |
author_sort | Cuyàs, Elisabet |
collection | PubMed |
description | The mitokine MOTS-c is a mitochondrially-encoded “exercise-mimetic peptide” expressed in multiple tissues, particularly skeletal muscles, which can be detected as a circulating hormone in the blood. MOTS-c mechanisms of action (MoA) involve insulin sensitization, enhanced glucose utilization, suppression of mitochondrial respiration, and targeting of the folate-AICAR-AMPK pathway. Although MOTS-c MoA largely overlap those of the anti-diabetic biguanide metformin, the putative regulatory actions of metformin on MOTS-c have not yet been evaluated in detail. Here, we measured circulating MOTS-c in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. We failed to find any significant alteration of circulating MOTS-c –as measured using the commercially available competitive ELISA CEX132Hu– in response to 24 weeks of a neoadjuvant chemotherapy/trastuzumab regimen with or without daily metformin. Changes in circulating MOTS-c levels failed to reach statistical significance when comparing patients achieving pathological complete response (pCR), irrespective of metformin treatment. The inability of metformin to target skeletal muscle, the major tissue for MOTS-c production and secretion, might limit its regulatory effects on circulating MOTS-c. Further studies are needed to definitely elucidate the nature of the interaction between metformin and MOTS-c in cancer and non-cancer patients. |
format | Online Article Text |
id | pubmed-10008497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-100084972023-03-13 Circulating levels of MOTS-c in patients with breast cancer treated with metformin Cuyàs, Elisabet Verdura, Sara Martin-Castillo, Begoña Menendez, Javier A. Aging (Albany NY) Research Perspective The mitokine MOTS-c is a mitochondrially-encoded “exercise-mimetic peptide” expressed in multiple tissues, particularly skeletal muscles, which can be detected as a circulating hormone in the blood. MOTS-c mechanisms of action (MoA) involve insulin sensitization, enhanced glucose utilization, suppression of mitochondrial respiration, and targeting of the folate-AICAR-AMPK pathway. Although MOTS-c MoA largely overlap those of the anti-diabetic biguanide metformin, the putative regulatory actions of metformin on MOTS-c have not yet been evaluated in detail. Here, we measured circulating MOTS-c in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. We failed to find any significant alteration of circulating MOTS-c –as measured using the commercially available competitive ELISA CEX132Hu– in response to 24 weeks of a neoadjuvant chemotherapy/trastuzumab regimen with or without daily metformin. Changes in circulating MOTS-c levels failed to reach statistical significance when comparing patients achieving pathological complete response (pCR), irrespective of metformin treatment. The inability of metformin to target skeletal muscle, the major tissue for MOTS-c production and secretion, might limit its regulatory effects on circulating MOTS-c. Further studies are needed to definitely elucidate the nature of the interaction between metformin and MOTS-c in cancer and non-cancer patients. Impact Journals 2022-12-06 /pmc/articles/PMC10008497/ /pubmed/36490309 http://dx.doi.org/10.18632/aging.204423 Text en Copyright: © 2023 Cuyàs et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Perspective Cuyàs, Elisabet Verdura, Sara Martin-Castillo, Begoña Menendez, Javier A. Circulating levels of MOTS-c in patients with breast cancer treated with metformin |
title | Circulating levels of MOTS-c in patients with breast cancer treated with metformin |
title_full | Circulating levels of MOTS-c in patients with breast cancer treated with metformin |
title_fullStr | Circulating levels of MOTS-c in patients with breast cancer treated with metformin |
title_full_unstemmed | Circulating levels of MOTS-c in patients with breast cancer treated with metformin |
title_short | Circulating levels of MOTS-c in patients with breast cancer treated with metformin |
title_sort | circulating levels of mots-c in patients with breast cancer treated with metformin |
topic | Research Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10008497/ https://www.ncbi.nlm.nih.gov/pubmed/36490309 http://dx.doi.org/10.18632/aging.204423 |
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