Title

Exosomes from Nischarin-Expressing Cells Reduce Breast Cancer Cell Motility and Tumor Growth.

Funding Source

National Institutes of Health

Grant Number

U54 GM104940

Department

Department of Biology

Document Type

Article

Publication Date

5-2019

Abstract

Exosomes are small extracellular microvesicles that are secreted by cells when intracellular multivesicular bodies fuse with the plasma membrane. We have previously demonstrated that Nischarin inhibits focal adhesion formation, cell migration, and invasion, leading to reduced activation of focal adhesion kinase. In this study, we propose that the tumor suppressor Nischarin regulates the release of exosomes. When cocultured on exosomes from Nischarin-positive cells, breast cancer cells exhibited reduced survival, migration, adhesion, and spreading. The same cocultures formed xenograft tumors of significantly reduced volumefollowing injectionintomice. Exosomes secreted by Nischarin-expressing tumors inhibited tumor growth. Expression of only one allele of Nischarin increased secretion of exosomes, and Rab14 activity modulated exosome secretions and cell growth. Taken together, this study reveals a novel role for Nischarin in preventing cancer cell motility, which contributes to our understanding of exosome biology. Significance: Regulation of Nischarin-mediated exosome secretion by Rab14 seems to play an important role in controlling tumor growth and migration.

Comments

DOI: 10.1158/0008-5472.CAN-18-0842

PubMed ID: 30635277

Funding text #1

  • We would like to thank the laboratory of Dr. Tarun Mandal at Xavier University of Louisiana for allowing us to use the Malvern Nanosight and the Beckman DelsaNanoC. Also, we thank the Fred Brazda Foundation and LSU School of Medicine for financial support.

  • Funding text #2

    D.E. Mercante was supported in part by U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Share

COinS