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Emerging Roles of the Endoplasmic Reticulum Associated Unfolded Protein Response in Cancer Cell Migration and Invasion

1,2,3,4,5,†, 1,2,†, 3,4, 3,4,5,6,7, 1,2,8 and 1,2,8,*
1
Proteostasis & Cancer Team, Institut National de la Santé Et la Recherche Médicale U1242 Chemistry, Oncogenesis, Stress and Signaling, Université de Rennes, 35042 Rennes, France
2
Centre Eugène Marquis, 35042 Rennes, France
3
Biomedical Neuroscience Institute, University of Chile, 8380453 Santiago, Chile
4
Center for Geroscience, Brain Health and Metabolism (GERO), 8380453 Santiago, Chile
5
Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, 8380453 Santiago, Chile
6
The Buck Institute for Research in Aging, Novato, CA 94945, USA
7
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
8
Rennes Brain Cancer Team (REACT), 35042 Rennes, France
*
Author to whom correspondence should be addressed.
Co-first authors.
Cancers 2019, 11(5), 631; https://doi.org/10.3390/cancers11050631
Received: 9 April 2019 / Revised: 29 April 2019 / Accepted: 1 May 2019 / Published: 6 May 2019
(This article belongs to the Special Issue Cellular Stress in Cancer Progression, Drug Resistance and Treatment)
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Abstract

Endoplasmic reticulum (ER) proteostasis is often altered in tumor cells due to intrinsic (oncogene expression, aneuploidy) and extrinsic (environmental) challenges. ER stress triggers the activation of an adaptive response named the Unfolded Protein Response (UPR), leading to protein translation repression, and to the improvement of ER protein folding and clearance capacity. The UPR is emerging as a key player in malignant transformation and tumor growth, impacting on most hallmarks of cancer. As such, the UPR can influence cancer cells’ migration and invasion properties. In this review, we overview the involvement of the UPR in cancer progression. We discuss its cross-talks with the cell migration and invasion machinery. Specific aspects will be covered including extracellular matrix (ECM) remodeling, modification of cell adhesion, chemo-attraction, epithelial-mesenchymal transition (EMT), modulation of signaling pathways associated with cell mobility, and cytoskeleton remodeling. The therapeutic potential of targeting the UPR to treat cancer will also be considered with specific emphasis in the impact on metastasis and tissue invasion. View Full-Text
Keywords: cancer; cell invasion; cell migration; ER stress; IRE1; PERK; ATF6 cancer; cell invasion; cell migration; ER stress; IRE1; PERK; ATF6
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Limia, C.M.; Sauzay, C.; Urra, H.; Hetz, C.; Chevet, E.; Avril, T. Emerging Roles of the Endoplasmic Reticulum Associated Unfolded Protein Response in Cancer Cell Migration and Invasion. Cancers 2019, 11, 631.

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