ArticleProceedings of the National Academy of Sciences of the United States of America2017
SGK3 sustains ERα signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Rat somatic genome editing enables ER+ breast cancer modeling.bioRxiv : the preprint server for biology · 2025Article
- The SGK3/GSK3β/β-catenin signaling promotes breast cancer stemness and confers resistance to alpelisib therapy.International journal of biological sciences · 2025Article
- SGK3 overexpression correlates with a poor prognosis in endoscopically resected superficial esophageal squamous cell neoplasia: A long-term study.World journal of gastroenterology · 2023Article
- AKTIP loss is enriched in ERα-positive breast cancer for tumorigenesis and confers endocrine resistance.Cell reports · 2022Article
- Huaier Induces Immunogenic Cell DeathFrontiers in cell and developmental biology · 2022Article
- Contributions of SGK3 to transporter-related diseases.Frontiers in cell and developmental biology · 2022Review
- Effects of PI3K inhibition in AI-resistant breast cancer cell lines: autophagy, apoptosis, and cell cycle progression.Breast cancer research and treatment · 2021Article
- Ionizing radiation downregulates estradiol synthesis via endoplasmic reticulum stress and inhibits the proliferation of estrogen receptor-positive breast cancer cells.Cell death & disease · 2021Article
- Amphiregulin retains ERα expression in acquired aromatase inhibitor resistant breast cancer cells.Endocrine-related cancer · 2020Article
- Role of the mitochondrial stress response in human cancer progression.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Neuroprotective Role of Akt in Hypoxia Adaptation in Andeans.Frontiers in neuroscience · 2020Article
- CCT020312 Inhibits Triple-Negative Breast Cancer Through PERK Pathway-Mediated G1 Phase Cell Cycle Arrest and Apoptosis.Frontiers in pharmacology · 2020Article
- Suppression of Nuclear Factor-κB by Glucocorticoid Receptor Blocks Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.Molecular cancer therapeutics · 2019Article
- Feedback Activation of SGK3 and AKT Contributes to Rapamycin Resistance by Reactivating mTORC1/4EBP1 Axis via TSC2 in Breast Cancer.International journal of biological sciences · 2019Article
- Modulation of nuclear factor-kappa B activation by the endoplasmic reticulum stress sensor PERK to mediate estrogen-induced apoptosis in breast cancer cells.Cell death discovery · 2018Article
- Serum and glucocorticoid inducible protein kinases (SGKs): a potential target for cancer intervention.Acta pharmaceutica Sinica. B · 2018Review
- Maresin 1 attenuates NAFLD by suppression of endoplasmic reticulum stress via AMPK-SERCA2b pathway.The Journal of biological chemistry · 2018Article
- Potential implication of SGK1-dependent activity change in BV-2 microglial cells.International journal of physiology, pathophysiology and pharmacology · 2018Article
- RNA sequencing identified novel target genes forScience progressArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Many estrogen receptor alpha (ERα)-positive breast cancers initially respond to aromatase inhibitors (AIs), but eventually acquire resistance. Here, we report that serum- and glucocorticoid-inducible kinase 3 (SGK3), a kinase transcriptionally regulated by ERα in breast cancer, sustains ERα signaling and drives acquired AI resistance. SGK3 is up-regulated and essential for endoplasmic reticulum (EnR) homeostasis through preserving sarcoplasmic/EnR calcium ATPase 2b (SERCA2b) function in AI-resistant cells. We have further found that EnR stress response down-regulates ERα expression through the protein kinase RNA-like EnR kinase (PERK) arm, and SGK3 retains ERα expression and signaling by preventing excessive EnR stress. Our study reveals regulation of ERα expression mediated by the EnR stress response and the feed-forward regulation between SGK3 and ERα in breast cancer. Given SGK3 inhibition reduces AI-resistant cell survival by eliciting excessive EnR stress and also depletes ERα expression/function, we propose SGK3 inhibition as a potential effective treatment of acquired AI-resistant breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.