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Flynn et al. J Cancer Metastasis Treat 2019;5:43 Journal of Cancer
DOI: 10.20517/2394-4722.2019.13 Metastasis and Treatment

Review Open Access

Autophagy in breast cancer metastatic dormancy:
tumor suppressing or tumor promoting functions?

Alyssa La Belle Flynn , William P. Schiemann 2
1
1 Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA.
2 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: william.schiemann@case.edu

How to cite this article: Flynn ALB, Schiemann WP. Autophagy in breast cancer metastatic dormancy: tumor suppressing or
tumor promoting functions? J Cancer Metastasis Treat 2019;5:43. http://dx.doi.org/10.20517/2394-4722.2019.13

Received: 5 Feb 2019 First Decision: 4 Mar 2019 Revised: 27 Mar 2019 Accepted: 16 Apr 2019 Published: 14 May 2019

Science Editor: Chun Hei Antonio Cheung Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Breast cancer is the second leading cause of cancer-associated death in women in the United States, with more than
90% of those deaths attributed to metastasis. Breast cancer metastasis is incurable and possesses few treatment
options and a poor overall prognosis due in part to confounding metastatic attributes, particularly the acquisition
of dormancy-associated phenotypes. Dormant disseminated tumor cells can persist for years-to-decades before
recurring as highly aggressive, secondary lesions. Dormancy-associated phenotypes are exhibited by breast cancer
stem cells (BCSCs), which undergo tumor initiation and unlimited self-renewal. In addition to their specialized
abilities to circumvent chemotherapeutic insults, BCSCs also upregulate autophagy during metastatic dormancy
as a means to survive in nutrient poor conditions and environmental stress. As such, therapeutic targeting of
autophagy is actively being pursued as an attractive strategy to alleviate metastatic disease and the recurrence of
dormant BCSCs. Here we review the molecular and cellular features of autophagy, as well as its paradoxical role in
both suppressing and promoting mammary tumor development and metastatic progression. Finally, we highlight
the clinical challenges associated with therapeutic targeting of autophagy in metastatic breast cancers.

Keywords: Autophagy, breast cancer, cancer stem cells, metastatic dormancy, metastatic relapse

INTRODUCTION
Breast cancer is the second deadliest malignancy in women, accounting for nearly 41,000 deaths in the
[1]
United States in 2018 . More than 90% of the deaths attributed to breast cancer are caused by metastasis,
[2]
a disease state associated with poor prognosis and little-to-no effective treatment options . Indeed, while
initial treatment of breast cancers can be effective and achieve remission, an estimated 30% of lymph

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
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