Journal Article

DKFZ-2026-01057

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png GLYATL1 is associated with metabolic and epigenetic changes and with endocrine resistance in luminal breast cancer.

Müller, J. (First author)DKFZ* ; Sofyali, E. (First author)DKFZ* ; Schwarzmüller, L. (First author)DKFZ* ; Aylon, Y. ; Weizman, E. ; Schlicker, L.DKFZ* ; Kelly, K.DKFZ* ; Borgoni, S.DKFZ* ; Öz, A. S.DKFZ* ; Stocker, C.DKFZ* ; Burmester, S.DKFZ* ; Wörner, A.DKFZ* ; Karolus, S.DKFZ* ; Michels, B.DKFZ* ; Heiss, D.DKFZ* ; Will, R.DKFZ* ; de Melo Costa, V. R.DKFZ* ; Lutsik, P.DKFZ* ; Weichenhan, D.DKFZ* ; Hofmann, I.DKFZ* ; Nataraj, N. B. ; Yarden, Y. ; Magnani, L. ; Plass, C.DKFZ* ; Schulze, A.DKFZ* ; Körner, C.DKFZ* ; Oren, M. ; Wiemann, S. (Last author)DKFZ*

2026
BioMed Central [Erscheinungsort nicht ermittelbar]

Abstract: Estrogen receptor alpha (ERα)-positive luminal breast cancer is commonly treated with aromatase inhibitors (AI) to block estrogen signaling; however, resistance frequently develops, limiting therapy success.We observed that GLYATL1 (Glycine-N-Acyltransferase Like 1) expression is upregulated in AI-resistant breast cancer cell models and in patients undergoing AI therapy, correlating with poorer survival. Here we demonstrate that GLYATL1 promotes resistance to estrogen deprivation by elevating succinate levels and altering epigenetic histone marks associated with active transcription. Knockdown or knockout of GLYATL1 reverses these effects and reduces proliferation under estrogen-deprived conditions. Notably, GLYATL1 expression is positively regulated by estrogen receptor alpha signaling, however, independently of estrogen.These findings reveal GLYATL1 as a metabolic and epigenetic mediator of endocrine therapy resistance, suggesting it as a potential target to overcome AI resistance in luminal breast cancer.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Breast Neoplasms: genetics (MeSH) ; Breast Neoplasms: drug therapy (MeSH) ; Breast Neoplasms: metabolism (MeSH) ; Epigenesis, Genetic (MeSH) ; Drug Resistance, Neoplasm: genetics (MeSH) ; Cell Line, Tumor (MeSH) ; Gene Expression Regulation, Neoplastic: drug effects (MeSH) ; Estrogen Receptor alpha: metabolism (MeSH) ; Estrogen Receptor alpha: genetics (MeSH) ; Aromatase Inhibitors: therapeutic use (MeSH) ; Aromatase Inhibitors: pharmacology (MeSH) ; MCF-7 Cells (MeSH) ; Up-Regulation (MeSH) ; Aromatase inhibition ; Endocrine therapy resistance ; Estrogen-receptor alpha (ERα) ; GLYATL1 ; Luminal breast cancer ; Estrogen Receptor alpha ; Aromatase Inhibitors

Note: #EA:B050#LA:B050#

---

Contributing Institute(s):

1. B050 Molekulare Genomanalyse (B050)
2. Zelluläre Tools (W111)
3. Epigenomik (B370)
4. Metabolismus und Microenvironment (A410)
5. Lehrveranstaltungen (W071)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

---

Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---