ArticleMolecular and cellular biology2013
Extracellular heat shock protein 90 signals through subdomain II and the NPVY motif of LRP-1 receptor to Akt1 and Akt2: a circuit essential for promoting skin cell migration in vitro and wound healing in vivo.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer.International journal of molecular sciences · 2021Trial
- Elucidating the Multi-Target Anti-Pruritic Mechanism ofCurrent issues in molecular biology · 2026Article
- Review
- Upregulation of HSP90α in the lungs and circulation in sarcoidosis.Frontiers in medicine · 2025Article
- Extracellular heat shock protein 90 alpha (eHsp90α)'s role in cancer progression and the development of therapeutic strategies.European journal of medicinal chemistry · 2024Review
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- Exosomes from Adipose Stem Cells Promote Diabetic Wound Healing through the eHSP90/LRP1/AKT Axis.Cells · 2022Article
- Extracellular HSP90α promotes cellular senescence by modulating TGF-β signaling in pulmonary fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- LRP-1 receptor combines EGFR signalling and eHsp90α autocrine to support constitutive breast cancer cell motility in absence of blood supply.Scientific reports · 2022Article
- Extracellular Heat Shock Protein-90 (eHsp90): Everything You Need to Know.Biomolecules · 2022Review
- Article
- The Therapeutic Roles of Recombinant Hsp90α on Cornea Epithelial Injury.Investigative ophthalmology & visual science · 2022Article
- Targeting extracellular Hsp90: A unique frontier against cancer.Frontiers in molecular biosciences · 2022Review
- Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes.BMJ open diabetes research & care · 2022Observational
- Wound Healing Driver Gene and Therapeutic Development: Political and Scientific Hurdles.Advances in wound care · 2021Review
- Inflammation, Extracellular Matrix Remodeling, and Proteostasis in Tumor Microenvironment.International journal of molecular sciences · 2021Review
- The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.Archives of toxicology · 2021Review
- Intense immunostaining of heat shock protein 70 within renal interstitium associates with long-term renal survival in an ANCA-associated vasculitis cohort.Cell stress & chaperones · 2021Article
- The Dual Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Atherosclerosis.Frontiers in cardiovascular medicine · 2021Review
- Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Normal cells secrete heat shock protein 90 alpha (Hsp90α) in response to tissue injury. Tumor cells have managed to constitutively secrete Hsp90α during invasion and metastasis. The sole function of extracellular Hsp90α (eHsp90α) is to promote cell motility, a critical event for both wound healing and tumor progression. The mechanism of promotility action by eHsp90α, however, has remained elusive. A key issue is whether eHsp90α still acts as a chaperone outside the cells or is a new and bona fide signaling molecule. Here, we have provided evidence that eHsp90α utilizes a unique transmembrane signaling mechanism to promote cell motility and wound healing. First, subdomain II in the extracellular part of low-density lipoprotein receptor-related protein 1 (LRP-1) receives the eHsp90α signal. Then, the NPVY but not the NPTY motif in the cytoplasmic tail of LRP-1 connects eHsp90α signaling to serine 473 but not threonine 308 phosphorylation in Akt kinases. Individual knockdown of Akt1, Akt2, or Akt3 revealed the importance of Akt1 and Akt2 in eHsp90α-induced cell motility. Akt gene rescue experiments suggest that Akt1 and Akt2 work in concert, rather than independently, to mediate eHsp90α promotility signaling. Finally, Akt1 and Akt2 knockout mice showed impaired wound healing that cannot be corrected by topical application with the eHsp90α protein.
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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.