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Tutanov et al. Extracell Vesicles Circ Nucleic Acids 2023;4:195-217 Extracellular Vesicles and
DOI: 10.20517/evcna.2023.17
Circulating Nucleic Acids

Review Open Access

Emerging connections between GPI-anchored
proteins and their extracellular carriers in colorectal

cancer

1,#
Oleg S. Tutanov , Sarah E. Glass 1,2,# , Robert J. Coffey 1
1
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
2
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.
#
Authors contributed equally.
Correspondence to: Robert J. Coffey, MD, Epithelial Biology Center, Vanderbilt University Medical Center, 10415 MRBIV,
Nashville 37232, USA. E-mail: robert.coffey@vumc.org
How to cite this article: Tutanov OS, Glass SE, Coffey RJ. Emerging connections between GPI-anchored proteins and their
extracellular carriers in colorectal cancer. Extracell Vesicles Circ Nucleic Acids 2023;4:195-217.
https://dx.doi.org/10.20517/evcna.2023.17

Received: 10 Mar 2023 First Decision: 4 Apr 2023 Revised: 6 Apr 2023 Accepted: 8 May 2023 Pubished: 18 May 2023
Academic Editor: Yoke Peng Loh Copy Editor: Yanbing Bai Production Editor: Yanbing Bai

Abstract
Although extracellular vesicles (EVs) were discovered over 40 years ago, there has been a resurgence of interest in
secreted vesicles and their attendant cargo as novel modes of intracellular communication. In addition to vesicles,
two amembranous nanoparticles, exomeres and supermeres, have been isolated and characterized recently. In this
rapidly expanding field, it has been challenging to assign cargo and specific functions to a particular carrier.
Refinement of isolation methods, well-controlled studies, and guidelines detailed by Minimal Information for
Studies of Extracellular Vesicles (MISEV) are being employed to “bring order to chaos.” In this review, we will
briefly summarize three types of extracellular carriers - small EVs (sEVs), exomeres, and supermeres - in the
context of colorectal cancer (CRC). We found that a number of GPI-anchored proteins (GPI-APs) are
overexpressed in CRC, are enriched in exosomes (a distinct subset of sEVs), and can be detected in exomeres and
supermeres. This affords the opportunity to elaborate on GPI-AP biogenesis, modifications, and trafficking using
DPEP1, a GPI-AP upregulated in CRC, as a prime example. We have cataloged the GPI-anchored proteins secreted
in CRC and will highlight features of select CRC-associated GPI-anchored proteins we have detected. Finally, we
will discuss the remaining challenges and future opportunities in studying these secreted GPI-APs in CRC.

Keywords: Extracellular vesicles, exosomes, exomeres, supermeres, GPI-anchored proteins, biomarkers, colorectal
cancer

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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