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Study · Animal study (in vivo) · mouse · 2025

6 results

Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.

Cui X, Zhu Y, Zeng L, Zhang M, Uddin A, Gillespie TW, McCullough LE, Zhao S, Torres MA, Wan Y

Advanced science (Weinheim, Baden-Wurttemberg, Germany)27 Jan 2025Cited by 18 (Europe PMC)

PMID39868848 (opens in a new tab)PMCIDPMC11923992 (opens in a new tab)DOI10.1002/advs.202407494 (opens in a new tab)PepBankPUB-39868848
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Summary

Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC. Mechanistically, cancer-associated adipocytes drive metabolic reprogramming resulting in an upregulated hexosamine biosynthetic pathway (HBP). This aberrant upregulation of HBP promotes YAP O-GlcNAcylation and the subsequent recruitment of EIF3H deubiquitinase, which stabilizes YAP, thus promoting tumor growth and chemotherapy resistance. It is found that Retatrutide, an anti-obesity agent, inhibits HBP and YAP O-GlcNAcylation leading to increased YAP degradation through the deprivation of EIF3H-mediated deubiquitylation of YAP. In preclinical models of obese TNBC, Retatrutide downregulates HBP, decreases YAP protein levels, and consequently decreases tumor size and enhances chemotherapy efficacy. This effect is particularly pronounced in obese mice bearing TNBC tumors. Overall, these findings reveal a critical interplay between adipocyte-mediated metabolic reprogramming and EIF3H-mediated YAP proteolytic control, offering promising therapeutic strategies to mitigate the adverse effects of obesity on TNBC progression.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In preclinical models of obese triple-negative breast cancer, retatrutide downregulated the hexosamine biosynthetic pathway.

    In plain wordsIn preclinical models of obese breast cancer, retatrutide lowered activity of the hexosamine biosynthetic pathway.

    Peptide
    Retatrutide
    Outcome
    DecreaseHexosamine biosynthetic pathway activity
    Study

    mousen: not reported in source

    Obese TNBC tumour models
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In preclinical models of obese TNBC, Retatrutide downregulates HBP, decreases YAP protein levels, and consequently decreases tumor size and enhances chemotherapy efficacy. This effect is particularly pronounced in obese mice bearing TNBC tumors.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In preclinical models of obese triple-negative breast cancer, retatrutide decreased YAP protein levels.

    In plain wordsIn preclinical models of obese breast cancer, retatrutide lowered levels of the YAP protein.

    Peptide
    Retatrutide
    Outcome
    DecreaseYAP protein level
    Study

    mousen: not reported in source

    Obese TNBC tumour models
    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In preclinical models of obese TNBC, Retatrutide downregulates HBP, decreases YAP protein levels, and consequently decreases tumor size and enhances chemotherapy efficacy. This effect is particularly pronounced in obese mice bearing TNBC tumors.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In preclinical models of obese triple-negative breast cancer, retatrutide decreased tumor size, with a particularly strong effect in obese mice.

    In plain wordsIn preclinical models of obese breast cancer, retatrutide shrank tumours, most clearly in obese mice.

    Peptide
    Retatrutide
    Outcome
    DecreaseTumor size
    Study

    mousen: not reported in source

    Obese TNBC tumour models
    Outcome group
    Tumor growth · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In preclinical models of obese TNBC, Retatrutide downregulates HBP, decreases YAP protein levels, and consequently decreases tumor size and enhances chemotherapy efficacy. This effect is particularly pronounced in obese mice bearing TNBC tumors.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In preclinical models of obese triple-negative breast cancer, retatrutide enhanced chemotherapy efficacy.

    In plain wordsIn preclinical models of obese breast cancer, retatrutide made chemotherapy work better.

    Peptide
    Retatrutide
    Outcome
    IncreaseChemotherapy efficacy
    Study

    mousen: not reported in source

    Obese TNBC tumour models
    Outcome group
    Tumor growth · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In preclinical models of obese TNBC, Retatrutide downregulates HBP, decreases YAP protein levels, and consequently decreases tumor size and enhances chemotherapy efficacy. This effect is particularly pronounced in obese mice bearing TNBC tumors.
  5. 05AnimalAnimal study (in vivo)Mechanism

    Retatrutide inhibited the hexosamine biosynthetic pathway and YAP O-GlcNAcylation in the study models.

    In plain wordsIn the study models, retatrutide reduced a chemical tag (O-GlcNAc) on the YAP protein.

    Peptide
    Retatrutide
    Outcome
    DecreaseYAP O-GlcNAcylation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    It is found that Retatrutide, an anti-obesity agent, inhibits HBP and YAP O-GlcNAcylation leading to increased YAP degradation through the deprivation of EIF3H-mediated deubiquitylation of YAP.
  6. 06AnimalAnimal study (in vivo)Mechanism

    Retatrutide increased YAP degradation by depriving YAP of EIF3H-mediated deubiquitylation in the study models.

    In plain wordsIn the study models, retatrutide led to more breakdown of the YAP protein.

    Peptide
    Retatrutide
    Outcome
    IncreaseYAP degradation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cancer
    Studied dose
    Dose not stated

    Source sentences

    Summary
    It is found that Retatrutide, an anti-obesity agent, inhibits HBP and YAP O-GlcNAcylation leading to increased YAP degradation through the deprivation of EIF3H-mediated deubiquitylation of YAP.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 19:08 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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