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Regulatory Roles of HSP90-Rich Extracellular Vesicles

  • Takanori EguchiEmail author
  • Kisho Ono
  • Kazumi Kawata
  • Kuniaki Okamoto
  • Stuart K. Calderwood
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 19)

Abstract

HSP90 is an essential protein in protein folding, cancer progression and wound healing. Originally, most studies were focused on the intracellular molecular chaperone role of HSP90. However, more recent studies, including ours, have reported the secretion of HSP90 and novel functions for this protein in the extracellular space (ex-HSP90). Additionally, HSP90 has been found to be a major cargo contained in extracellular vesicles (EV) such as exosomes. HSP90 can directly bind to and promote functions of CD91/LRP1 and receptor tyrosine kinases such as EGF receptor. HSP90 also regulates the recycling of Rab proteins that control the secretion of exosomes. This chapter reviews current knowledge and the future potential of ex-HSP90 and EV-HSP90.

Keywords

Ectosome Epithelial-mesenchymal transition Exosome Extracellular matrix Extracellular vesicle HSP90 LRP1/CD91 Rab proteins 

Abbreviations

ECM

Extracellular matrix

EGFR

Epidermal growth factor receptor

EMT

Epithelial-mesenchymal transition

EV

Extracellular vesicle

ex-HSP90

Extracellular HSP90

FN

Fibronectin

HIF-1

Hypoxia-inducible factor-1

HNC

Head and neck cancer

HSP

Heat shock protein

ic-HSP90

Intracellular HSP90

LRP1

Lipoprotein receptor-related protein 1

MV

Microvesicle

MVB

Multivesicular body

OSCC

Oral squamous cell carcinoma

RTK

Receptor tyrosine kinase

TM

Transmembrane

TSP1

Thrombospondin 1

Notes

Acknowledgements

This paper is dedicated to the memory of one of our mentors, Professor Ken-ichi Kozaki, who passed away on May 29, 2016. The authors thank Yuka Okusha, Chiharu Sogawa, Masaharu Takigawa, Sati Kubota, Akira Sasaki, Ayesha Murshid, Thomas Prince, and Benjamin Lang for useful discussion and helpful suggestion. This work was supported by JSPS KAKENHI, grant numbers JP17K11642 (TE), JP17K11643 (TE), JP17K11669 (TE), JP16K11863 (KOk), JP18K09789 (TE) and by SUZUKEN memorial foundation (TE).

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Takanori Eguchi
    • 1
    • 2
    Email author
  • Kisho Ono
    • 1
    • 3
  • Kazumi Kawata
    • 4
  • Kuniaki Okamoto
    • 1
  • Stuart K. Calderwood
    • 5
  1. 1.Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
  2. 2.Advanced Research Center for Oral and Craniofacial Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
  3. 3.Department of Oral and Maxillofacial SurgeryOkayama University HospitalOkayamaJapan
  4. 4.Department of Biochemistry and Molecular Dentistry, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
  5. 5.Department of Radiation Oncology, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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