Hyaluronidase Hyal1 increases tumor cell proliferation and motility through accelerated vesicle trafficking

Caitlin O. McAtee, Abigail R. Berkebile, Christian G. Elowsky, Teresa Fangman, Joseph J. Barycki, James K Wahl, Oleh Khalimonchuk, Naava Naslavsky, Steven H Caplan, Melanie A. Simpson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Hyaluronan (HA) turnover accelerates metastatic progression of prostate cancer in part by increasing rates of tumor cell proliferation and motility. To determine the mechanism, we overexpressed hyaluronidase 1 (Hyal1) as a fluorescent fusion protein and examined its impact on endocytosis and vesicular trafficking. Overexpression of Hyal1 led to increased rates of internalization of HA and the endocytic recycling marker transferrin. Live imaging of Hyal1, sucrose gradient centrifugation, and specific colocalization of Rab GTPases defined the subcellular distribution of Hyal1 as early and late endosomes, lysosomes, and recycling vesicles. Manipulation of vesicular trafficking by chemical inhibitors or with constitutively active and dominant negative Rab expression constructs caused atypical localization of Hyal1. Using the catalytically inactive point mutant Hyal1-E131Q, we found that enzymatic activity of Hyal1 was necessary for normal localization within the cell as Hyal1-E131Q was mainly detected within the endoplasmic reticulum. Expression of a HA-binding point mutant, Hyal1-Y202F, revealed that secretion of Hyal1 and concurrent reuptake from the extracellular space are critical for rapid HA internalization and cell proliferation. Overall, excess Hyal1 secretion accelerates endocytic vesicle trafficking in a substrate-dependent manner, promoting aggressive tumor cell behavior.

Original languageEnglish (US)
Pages (from-to)13144-13156
Number of pages13
JournalJournal of Biological Chemistry
Volume290
Issue number21
DOIs
StatePublished - May 22 2015

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Hyaluronoglucosaminidase
Cell proliferation
Cell Movement
Tumors
Cell Proliferation
Neoplasms
Hyaluronic Acid
Recycling
rab GTP-Binding Proteins
Transport Vesicles
Centrifugation
Endosomes
Extracellular Space
Transferrin
Endocytosis
Lysosomes
Endoplasmic Reticulum
Sucrose
Prostatic Neoplasms
Fusion reactions

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

McAtee, C. O., Berkebile, A. R., Elowsky, C. G., Fangman, T., Barycki, J. J., Wahl, J. K., ... Simpson, M. A. (2015). Hyaluronidase Hyal1 increases tumor cell proliferation and motility through accelerated vesicle trafficking. Journal of Biological Chemistry, 290(21), 13144-13156. https://doi.org/10.1074/jbc.M115.647446

Hyaluronidase Hyal1 increases tumor cell proliferation and motility through accelerated vesicle trafficking. / McAtee, Caitlin O.; Berkebile, Abigail R.; Elowsky, Christian G.; Fangman, Teresa; Barycki, Joseph J.; Wahl, James K; Khalimonchuk, Oleh; Naslavsky, Naava; Caplan, Steven H; Simpson, Melanie A.

In: Journal of Biological Chemistry, Vol. 290, No. 21, 22.05.2015, p. 13144-13156.

Research output: Contribution to journalArticle

McAtee, Caitlin O. ; Berkebile, Abigail R. ; Elowsky, Christian G. ; Fangman, Teresa ; Barycki, Joseph J. ; Wahl, James K ; Khalimonchuk, Oleh ; Naslavsky, Naava ; Caplan, Steven H ; Simpson, Melanie A. / Hyaluronidase Hyal1 increases tumor cell proliferation and motility through accelerated vesicle trafficking. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 21. pp. 13144-13156.
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