ArticleOncogene2013
Annexin A6 is a scaffold for PKCα to promote EGFR inactivation.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
51 citing papers in PubMed, 71 citations in OpenAlex.
- Annexin A6 controls multi-organelle contact site formation and endolysosomal positioning, and remodels the STARD3 interactome.iScience · 2026Article
- Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C Disease.Pharmaceutical research · 2026Article
- The Multifaceted Role of Annexin A1 in Colorectal Cancer: From Molecular Mechanisms to Predictive and Prognostic Implications.Medical sciences (Basel, Switzerland) · 2025Review
- Integration of machine learning to reveal the correlation between ferroptosis and M2 macrophages in head and neck squamous cell carcinoma.Discover oncology · 2025Article
- Revisiting the role of Annexins in membrane trafficking.Cellular and molecular life sciences : CMLS · 2025Review
- ANXA1 promotes intrahepatic cholangiocarcinoma proliferation and growth by regulating glutamine metabolism through GOT1 stabilization.Journal of experimental & clinical cancer research : CR · 2025Article
- Injectable sustainable andrographolide-releasing hydrogel for long-lasting alleviation of osteoarthritis and regulation of chondrocyte autophagy via PRKCA/EGFR.Materials today. Bio · 2025Article
- Identification of Core SASP-Related Genes TGFBI and ANXA6 for Diagnosing Ulcerative Colitis-Related Colorectal Cancer Through Machine Learning.Journal of inflammation research · 2025Article
- Annexin A: Cell Death, Inflammation, and Translational Medicine.Journal of inflammation research · 2025Review
- Annexins-a family of proteins with distinctive tastes for cell signaling and membrane dynamics.Nature communications · 2024Review
- Cross talk of tumor protein D52 (TPD52) with KLF9, PKCε, and MicroRNA 223 in ovarian cancer.Journal of ovarian research · 2023Article
- SUMOylation of AnxA6 facilitates EGFR-PKCα complex formation to suppress epithelial cancer growth.Cell communication and signaling : CCS · 2023Article
- ANXA6: a key molecular player in cancer progression and drug resistance.Discover oncology · 2023Review
- Article
- Endoglin and MMP14 Contribute to Ewing Sarcoma Spreading by Modulation of Cell-Matrix Interactions.International journal of molecular sciences · 2022Article
- Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance.International journal of molecular sciences · 2022Review
- Article
- Annexin A6 and NPC1 regulate LDL-inducible cell migration and distribution of focal adhesions.Scientific reports · 2022Article
- Pathobiological functions and clinical implications of annexin dysregulation in human cancers.Frontiers in cell and developmental biology · 2022Review
- Exosomal annexin A6 induces gemcitabine resistance by inhibiting ubiquitination and degradation of EGFR in triple-negative breast cancer.Cell death & disease · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase Cα (PKCα) can phosphorylate the epidermal growth factor receptor (EGFR) at threonine 654 (T654) to inhibit EGFR tyrosine phosphorylation (pY-EGFR) and the associated activation of downstream effectors. However, upregulation of PKCα in a large variety of cancers is not associated with EGFR inactivation, and factors determining the potential of PKCα to downregulate EGFR are yet unknown. Here, we show that ectopic expression of annexin A6 (AnxA6), a member of the Ca(2+) and phospholipid-binding annexins, strongly reduces pY-EGFR levels while augmenting EGFR T654 phosphorylation in EGFR overexpressing A431, head and neck and breast cancer cell lines. Reduced EGFR activation in AnxA6 expressing A431 cells is associated with reduced EGFR internalization and degradation. RNA interference (RNAi)-mediated PKCα knockdown in AnxA6 expressing A431 cells reduces T654-EGFR phosphorylation, but restores EGFR tyrosine phosphorylation, clonogenic growth and EGFR degradation. These findings correlate with AnxA6 interacting with EGFR, and elevated AnxA6 levels promoting PKCα membrane association and interaction with EGFR. Stable expression of the cytosolic N-terminal mutant AnxA6(1-175), which cannot promote PKCα membrane recruitment, does not increase T654-EGFR phosphorylation or the association of PKCα with EGFR. AnxA6 overexpression does not inhibit tyrosine phosphorylation of the T654A EGFR mutant, which cannot be phosphorylated by PKCα. Most strikingly, stable plasma membrane anchoring of AnxA6 is sufficient to recruit PKCα even in the absence of EGF or Ca(2+). In summary, AnxA6 is a new PKCα scaffold to promote PKCα-mediated EGFR inactivation through increased membrane targeting of PKCα and EGFR/PKCα complex formation.
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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.