Circulating levels of MOTS-c in patients with breast cancer treated with metformin.

Cuyàs E, Verdura S, Martin-Castillo B, Menendez JA

Aging6 Dec 2022Cited by 4 (Europe PMC)

PMID36490309PMCIDPMC10008497DOI10.18632/aging.204423PepBankPUB-36490309

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

No result from this study comes from a test of the peptide.

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01HumanEndogenous levelRandomized controlled trialOther
In patients with HER2-positive breast cancer, circulating MOTS‑c showed no significant change after 24 weeks of chemotherapy and trastuzumab, with or without daily metformin.
In plain wordsIn patients with HER2-positive breast cancer, the body's own MOTS‑c in blood did not change significantly with chemotherapy, with or without metformin.
Peptide
MOTS-c
Outcome
No significant changeChange in circulating MOTS-c over 24 weeks of chemotherapy and trastuzumab with or without metformin
Study
n: not reported in source
Comparator
Regimen without metformin
Outcome group
Aging markers · Cancer
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3649030901
02HumanEndogenous levelRandomized controlled trialOther
In patients with HER2-positive breast cancer, changes in circulating MOTS‑c did not differ significantly between patients with and without pathological complete response, irrespective of metformin.
In plain wordsIn patients with breast cancer, changes in the body's own MOTS‑c were not linked to a complete response to treatment.
Peptide
MOTS-c
Outcome
No significant changeChange in circulating MOTS-c by pathological complete response
Study
n: not reported in source
Comparator
Patients without pathological complete response
Outcome group
Aging markers · Cancer
Source sentences
Summary
Changes in circulating MOTS-c levels failed to reach statistical significance when comparing patients achieving pathological complete response (pCR), irrespective of metformin treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3649030902

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Version history

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Version 2Current
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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