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Maisel et al. J Cancer Metastasis Treat 2019;5:7 Journal of Cancer
DOI: 10.20517/2394-4722.2018.82 Metastasis and Treatment

Review Open Access

Wrong place at the wrong time: how retrograde
trafficking drives cancer metastasis through

receptor mislocalization

Sabrina A. Maisel , Joyce Schroeder 1,2,3
1
1 Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85724, USA.
2 Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
3 BIO5 Institute, Tucson, AZ 85724, USA.

Correspondence to: Dr. Joyce Schroeder, Arizona Cancer Center, University of Arizona, 1515 N Campbell Ave 3945A, Tucson,
AZ 85724, USA. E-mail: joyces@email.arizona.edu

How to cite this article: Maisel SA, Schroeder J. Wrong place at the wrong time: how retrograde trafficking drives cancer
metastasis through receptor mislocalization. J Cancer Metastasis Treat 2019;5:7.
http://dx.doi.org/10.20517/2394-4722.2018.82

Received: 30 Nov 2018 First Decision: 30 Dec 2018 Revised: 1 Jan 2019 Accepted: 4 Jan 2019 Published: 13 Feb 2019

Science Editor:William Schiemann Copy Editor: Cui Yu Production Editor: Huan-Liang Wu

Abstract
Retrograde trafficking is a well-regulated, multi-component pathway that can result in endosomal trafficking to
the trans-Golgi network, the perinuclear space, or the nucleus. Either clathrin or the retromer complex can travel
with proteins endocytosed from the plasma membrane, guided by Rabs (including 5, 6, 7, 9, 22A), interacting with
a host of sorting nexin proteins, and fusing with Golgi-specific anchors to allow transport of activated receptor
tyrosine kinases to a potential end within the nucleus. Amplification in these constituents is common in cancer,
leading to increased retrotranslocation and a reduction in degradation of receptor tyrosine kinases, an event highly
associated with cancer metastasis. Here, we review the role of retrograde trafficking in altering transmembrane
receptor localization and activity and the relationship to metastasis, focusing on all four members of the ErbB
family, with comparison to other receptor tyrosine kinases including the insulin receptor and fibroblast growth
factor receptor, as well as other transmembrane proteins dysregulated in metastasis. By examining how these
receptors are being alternatively trafficked and the cancer-associated events resulting from this process, we hope
to identify novel therapeutic targets.

Keywords: Retrograde trafficking, receptor tyrosine kinase, metastasis, nuclear receptor

© The Author(s) 2019. 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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