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Melanoma and the Unfolded Protein Response

School of Molecular Bioscience, The University of Sydney, Darlington 2006, Australia
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Chyi-Chia Richard Lee
Cancers 2016, 8(3), 30;
Received: 23 June 2015 / Revised: 3 February 2016 / Accepted: 18 February 2016 / Published: 27 February 2016
(This article belongs to the Special Issue Current Topics in Cutaneous Melanoma)
PDF [1129 KB, uploaded 27 February 2016]


The UPR (unfolded protein response) has been identified as a key factor in the progression and metastasis of cancers, notably melanoma. Several mediators of the UPR are upregulated in cancers, e.g., high levels of GRP78 (glucose-regulator protein 78 kDa) correlate with progression and poor outcome in melanoma patients. The proliferative burden of cancer induces stress and activates several cellular stress responses. The UPR is a tightly orchestrated stress response that is activated upon the accumulation of unfolded proteins within the ER (endoplasmic reticulum). The UPR is designed to mediate two conflicting outcomtes, recovery and apoptosis. As a result, the UPR initiates a widespread signaling cascade to return the cell to homeostasis and failing to achieve cellular recovery, initiates UPR-induced apoptosis. There is evidence that ER stress and subsequently the UPR promote tumourigenesis and metastasis. The complete role of the UPR has yet to be defined. Understanding how the UPR allows for adaption to stress and thereby assists in cancer progression is important in defining an archetype of melanoma pathology. In addition, elucidation of the mechanisms of the UPR may lead to development of effective treatments of metastatic melanoma. View Full-Text
Keywords: melanoma; unfolded protein response; UPR; ER stress melanoma; unfolded protein response; UPR; ER stress

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Sykes, E.K.; Mactier, S.; Christopherson, R.I. Melanoma and the Unfolded Protein Response. Cancers 2016, 8, 30.

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