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Robinson et al. J Cancer Metastasis Treat 2019;5:39 Journal of Cancer
DOI: 10.20517/2394-4722.2019.15 Metastasis and Treatment

Review Open Access

Stem cells, immortality, and the evolution of
metastatic properties in breast cancer: telomere

maintenance mechanisms and metastatic evolution

Nathaniel J. Robinson , Derek J. Taylor , William P. Schiemann 3
2
1
1 Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
2 Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
3 Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.

Correspondence to: Dr. William P. Schiemann, Case Comprehensive Cancer Center, Case Western Reserve University, Wolstein
Research Building, Room 2131, 2103 Cornell Road Cleveland, OH 44106, USA. E-mail: wps20@case.edu

How to cite this article: Robinson NJ, Taylor DJ, Schiemann WP. Stem cells, immortality, and the evolution of metastatic
properties in breast cancer: telomere maintenance mechanisms and metastatic evolution. J Cancer Metastasis Treat 2019;5:39.
http://dx.doi.org/10.20517/2394-4722.2019.15

Received: 8 Feb 2019 First Decision: 13 Mar 2019 Revised: 2 Apr 2019 Accepted: 8 Apr 2019 Published: 6 May 2019

Science Editor: Ya-Guang Xi Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Breast cancer is the most significant cause of cancer-related death in women around the world. The vast majority of
breast cancer-associated mortality stems from metastasis, which remains an incurable disease state. Metastasis results
from evolution of clones that possess the insidious properties required for dissemination and colonization of distant
organs. These clonal populations are descended from breast cancer stem cells (CSCs), which are also responsible for
their prolonged maintenance and continued evolution. Telomeres impose a lifespan on cells that can be extended when
they are actively elongated, as occurs in CSCs. Thus, changes in telomere structure serve to promote the survival of
CSCs and subsequent metastatic evolution. The selection of telomere maintenance mechanism (TMM) has important
consequences not only for CSC survival and evolution, but also for their coordination of various signaling pathways
that choreograph the metastatic cascade. Targeting the telomere maintenance machinery may therefore provide a
boon to the treatment of metastatic breast cancer. Here we review the two major TMMs and the roles they play in the
development of stem and metastatic breast cancer cells. We also highlight current and future approaches to targeting
these mechanisms in clinical settings to alleviate metastatic breast cancers.

Keywords: Breast cancer, cancer evolution, cancer stem cells, metastasis, telomerase

© 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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