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Cited by 46Endometriosis Research and TreatmentReproductive System and PregnancyReproductive Biology and Fertility

Loss of MIG-6 results in endometrial progesterone resistance via ERBB2

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Yoo, Jung-Yoon, Kim, Tae Hoon, Shin, Jung-Ho, Marquardt, Ryan M., Müller, Ulrich, Fazleabas, Asgerally T., Young, Steven L., Lessey, Bruce A. +2 more·2022·Nature Communications
DOI 10.1038/s41467-022-28608-xPMC PMC8888616

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Abstract

Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice ( Pgr cre/+ Mig-6 f/f ; Mig-6 d/d ). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6 d/d mice ( Mig-6 d/d Erbb2 d/d mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6 d/d mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6 d/d mice revert to their normal expression in Mig-6 d/d Erbb2 d/d mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects.

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  • ERRFI1 is associated with tumor development and drug resistance.

    “Given that ERRFI1 is associated with tumor development and drug resistance [29, 39, 40]”

    From Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRASG12D-mutated colorectal cancer (2023) · cites this paper as [40]

    The Results section links MIG-6 loss to increased endometriotic lesions, and the paper examines resistance to progesterone in the endometrium. Neither is evidence for the attributed association with tumor development and drug resistance. Searches for tumor development and drug resistance found no passage in our copy that addresses that claim. (LLM, conf=0.76)

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Authors
Yoo, J.-Y., Kim, T. H., Shin, J.-H., Marquardt, R. M., Müller, U., Fazleabas, A. T., Young, S. L., Lessey, B. A., Yoon, H.-G., & Jeong, J.-W.
Affiliations
  • Yonsei University Mirae Campus (KR)
  • Michigan State University (US)
  • Korea University Medical Center (KR)
  • Johns Hopkins University (US)
  • University of North Carolina at Chapel Hill (US)
  • Atrium Health Wake Forest Baptist (US)
  • Yonsei University (KR)
Corresponding author
  • Yoon, Ho-Geun
  • Jeong, Jae-Wook
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-03-01
Volume
13
Issue
1
Pages
1101-1101
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-28608-x
PMC
PMC8888616
OpenAlex
W4220758980
Cited by
46
References
67
Citations by year
2026: 8 · 2025: 13 · 2024: 15 · 2023: 8 · 2022: 2
FWCI
8.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders
U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD084478, R01HD101243)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords
MIG6, ERBB2, endometriosis, female subfertility, endometrial receptivity, progesterone signaling
MeSH terms
Animals, Endometriosis, Endometrium, Female, Infertility, Female, Progesterone, Receptors, Progesterone, Uterine Diseases, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Intracellular Signaling Peptides and Proteins, Mice

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