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Review
. 2020 Apr 26;9(5):1256.
doi: 10.3390/jcm9051256.

Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression

Wook Jin  1
Affiliations
Review

Novel Insights into PARK7 (DJ-1), a Potential Anti-Cancer Therapeutic Target, and Implications for Cancer Progression

Wook Jin. J Clin Med. .

Abstract

The expression of PARK7 is upregulated in various types of cancer, suggesting its potential role as a critical regulator of the pathogenesis of cancer and in the treatment of cancer and neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and Huntington disease. PARK7 activates various intracellular signaling pathways that have been implicated in the induction of tumor progression, which subsequently enhances tumor initiation, continued proliferation, metastasis, recurrence, and resistance to chemotherapy. Additionally, secreted PARK7 has been identified as a high-risk factor for the pathogenesis and survival of various cancers. This review summarizes the current understanding of the correlation between the expression of PARK7 and tumor progression.

Keywords: PARK7 (DJ-1); apoptosis; chemoresistance; redox sensor; therapeutic target.

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Conflict of interest statement

The author declares no conflict of interests.

Figures

Figure 1
Figure 1
(A) PARK7 induces tumor progression by permitting tumor initiation, continued proliferation, metastasis, recurrence, and resistance to chemotherapy by activating several intrinsic cell signaling pathways and upregulating the expression of oncoproteins. PARK7 activates the Hedgehog, Wnt, AKT, extracellular-signal-regulated kinase (ERK), and STAT3 signaling pathways and induces the expression of Krűppel-like transcription factor (KLF6/KLF17), which subsequently enhances tumor progression. (B) The upregulation of PARK7 expression serves as a sensor of oxidative stress and protects cancer cells from oxidative stress-induced apoptosis by inducing GABPA and thioredoxin (TXN), or by suppressing the TNFSF10-induced generation of intracellular reactive oxygen species (ROS).
Figure 2
Figure 2
PARK7 enhances the proliferation and aggressiveness of cancer cells by regulating the activity of several proteins via direct interactions. PARK7 binds to oncoproteins and tumor suppressors to regulate their activation, stabilization, and cellular localization. This subsequently enhances the metastatic potential of cancer cells and protects them from apoptosis and autophagy.
See this image and copyright information in PMC

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