ArticleAutophagy2020
Stabilization of MORC2 by estrogen and antiestrogens through GPER1- PRKACA-CMA pathway contributes to estrogen-induced proliferation and endocrine resistance of breast cancer cells.
Article in Autophagy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- Targeting MORC2 activates transposable element-mediated viral mimicry and potentiates immune checkpoint blockade in triple-negative breast cancer.Molecular cancer · 2026Article
- Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.Biology of sex differences · 2026Review
- CircKIAA1617 promotes stemness via USP14/PGRMC1-mediated autophagy and lipid metabolism reprogramming in ER-positive breast cancer.Molecular cancer · 2026Article
- Cold atmospheric plasma restores fulvestrant sensitivity by inhibiting CCND3 in the drug-resistant breast cancer cells.Scientific reports · 2025Article
- Astrocyte Autophagy in Neurodegenerative Diseases: Current Progress in Mechanisms and Therapeutics.Neurochemical research · 2025Review
- Comprehensive Network pharmacology and in vitro investigation of L-mimosine: unveiling multi-targeted therapeutic potential against breast cancer.BMC complementary medicine and therapies · 2025Article
- Estradiol rescues male hydroxyl radical-mediated Charcot-Marie-Tooth 2Z by Morc2a stabilization through autophagy inhibition in a murine model.Acta neuropathologica · 2025Article
- A select inhibitor of MORC2 encapsulated by chimeric membranecoated DNA nanocage target alleviation TNBC progression.Materials today. Bio · 2025Article
- Comprehensive analysis of molecular characteristics between primary and breast-derived metastatic ovarian cancer.Translational cancer research · 2025Article
- RBMS1-HSPA8 axis activation drives head and neck squamous cell carcinoma progression.BMC cancer · 2025Article
- Expression significance of biomarker MORC4 in colorectal cancer patients and its relationship with pathological features and prognosis.World journal of gastrointestinal oncology · 2025Article
- Secernin-2 Stabilizes Histone Methyltransferase KMT2C to Suppress Progression and Confer Therapeutic Sensitivity to PARP Inhibition in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Missense mutations of GPER1 in breast invasive carcinoma: Exploring gene expression, signal transduction and immune cell infiltration with insights from cellular pharmacology.Biomedical reports · 2025Article
- Selective protein degradation through chaperone‑mediated autophagy: Implications for cellular homeostasis and disease (Review).Molecular medicine reports · 2025Review
- Multiple regulatory mechanisms, functions and therapeutic potential of chaperone-mediated autophagy.Theranostics · 2025Review
- Pan-cancer analyses reveal cancer-type-specific autophagy signatures with potential implications for prognosis and therapy response.Journal of Cancer · 2025Article
- Biological functions and molecular mechanisms of MORC2 in human diseases.Molecules and cells · 2025Review
- Emerging roles of the chromatin remodeler MORC2 in cancer metabolism.Medical oncology (Northwood, London, England) · 2024Review
- Oncogenic MORC2 in cancer development and beyond.Genes & diseases · 2024Review
- GPER1 signaling restricts macrophage proliferation and accumulation in human hepatocellular carcinoma.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of estrogen signaling through three ESR (estrogen receptor) subtypes, termed ESR1/ERα, ESR2/ERβ, and GPER1 (G protein-coupled estrogen receptor 1), is implicated in breast cancer pathogenesis and progression. Antiestrogens tamoxifen (TAM) and fulvestrant (FUL) are effective for treatment of ESR1-positive breast tumors, but development of resistance represents a major clinical challenge. However, the molecular mechanisms behind these events remain largely unknown. Here, we report that 17β-estradiol (E2), TAM, and FUL stabilize MORC2 (MORC family CW-type zinc finger 2), an emerging oncoprotein in human cancer, in a GPER1-dependent manner. Mechanistically, GPER1 activates PRKACA (protein kinase cAMP-activated catalytic subunit alpha), which in turn phosphorylates MORC2 at threonine 582 (T582). Phosphorylated MORC2 decreases its interaction with HSPA8 (heat shock protein family A [Hsp70] member 8) and LAMP2A (lysosomal associated membrane protein 2A), two core components of the chaperone-mediated autophagy (CMA) machinery, thus protecting MORC2 from lysosomal degradation by CMA. Functionally, knockdown of ABBREVIATIONS: 4-OHT: 4-hydroxytamoxifen; Baf A1: bafilomycin A
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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.