Moving beyond the Tip of the Iceberg: DJ-1 Implications in Cancer Metabolism

Abstract

DJ-1, also called Parkinson’s protein 7 (PARK7), is ubiquitously expressed and plays multiple actions in different physiological and, especially, pathophysiological processes, as evidenced by its identification in neurodegenerative diseases and its high expression in different types of cancer. To date, the exact activity of DJ-1 in carcinogenesis has not been fully elucidated, however several recent studies disclosed its involvement in regulating fundamental pathways involved in cancer onset, development, and metastatization. At this purpose, we have dissected the role of DJ-1 in maintaining the transformed phenotype, survival, drug resistance, metastasis formation, and differentiation in cancer cells. Moreover, we have discussed the role of DJ-1 in controlling the redox status in cancer cells, along with the ability to attenuate reactive oxygen species (ROS)-dependent cell death, as well as to mediate ferropotosis. Finally, a mention to the development of therapeutic strategies targeting DJ-1 has been done. We have reported the most recent studies, aiming to shed light on the role played by DJ-1 in different cancer aspects and create the foundation for moving beyond the tip of the iceberg.

Development of Inhibitors, Probes, and PROTAC Provides a Complete Toolbox to Study PARK7 in the Living Cell

“…It should be noted that the covalent, irreversible nature of JYQ-194 may limit its potency as it cannot be recycled upon PARK7 degradation, which possibly lowers its efficacy in an in vivo setting . Despite its limitation, the creation of JYQ-194 PROTAC provides new opportunities for targeting PARK7 in cancer therapy since PARK7 is overexpressed in various types of cancer. ,, …”

“… 31 Despite its limitation, the creation of JYQ-194 PROTAC provides new opportunities for targeting PARK7 in cancer therapy since PARK7 is overexpressed in various types of cancer. 1 , 5 , 48 …”

“…Human Parkinson disease protein 7 (PARK7), also known as DJ-1, is a small (∼20 kDa) multifunctional protein, , which is associated with various types of cancer and Parkinson’s disease. − Throughout the years, PARK7 has been found to play a major role in protecting cells from stress conditions, especially oxidative stress, via its enzymatic and nonenzymatic functions . The key element for PARK7 functioning is the highly conserved cysteine residue at position 106.…”

miR-199a/b-3p inhibits HCC cell proliferation and invasion through a novel compensatory signaling pathway DJ-1\Ras\PI3K/AKT

“…The expression of DJ-1 gene can not only be used as a marker for mental cognitive diseases (such as Parkinson's disease, Alzheimer's disease 12 , 13 ), but also participate in the occurrence and progression of various tumors (thyroid cancer 20 , ovarian cancer 41 , colon cancer 14 , 16 , 21 , liver cancer 25 – 31 , lung cancer 22 , 23 , renal clear cell carcinoma 42 , breast cancer 17 ). Since Zhang D et al first found that the expression of DJ-1 is associated with the occurrence of HCC associated with HBV infection 43 , the role of DJ-1 in the proliferation, invasion and metastasis of HCC 25 – 30 , has been paid more and more attention by researchers, and it is regarded as a potential oncogene therapy target for HCC 15 . In this study, we first analyzed the expression level of DJ-1 in TCGA database and clinical HCC tissue samples, and the results showed that the expression of DJ-1 in TCGA database and HCC tissue samples was significantly higher than that of normal tissues and paracancerous tissues, and was closely related to the clinical stage T (T1T2 vs T3T4), pathological grade (I II vs III IV.)…”

Connexin 43 mediated collective cell migration is independent of Golgi orientation

“…The probable cause of the activation of EMT is due to the activation of the Wnt/β-catenin signalling pathway, which plays a fundamental role in determining the cell fate during early embryonic development along with the regulation of proliferation, and survival and apoptosis ( Liu et al, 2022 ). However, mutation of the Wnt pathway can lead to cancer due to the activation of the multifunctional protein DJ-1 ( Olivo et al, 2022 ). Our current experiment focused mainly on the relationship between Cx43, DJ-1 and EMT responsible for causing more migration in HeLa 43 cells however the mechanism of how DJ-1 activates the Wnt pathway by inhibiting β-catenin and thereby promoting EMT was not further investigated.…”