Knockdown of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition

He, Xiangyi; Sun, Yifeng; Fan, Rong; Sun, Jing Ping; Zou, Douwu; Yuan, Yaozong

doi:10.1016/j.omto.2021.01.013

Cited by 10 publications

(4 citation statements)

References 19 publications

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“…When phosphorylated, DJ-1 increases its glyoxalase activity preventing glycation-induced histones mis-regulation and preserving the epigenome landscape and, in the case of cancer cells, sustaining proliferation [11]. More recently, DJ-1 has been shown to mediate the development of multiple drug resistance (i.e., cancer cells) [12] by activating the PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating anti-apoptotic genes [13]. However, its role in responding to oxidative stress is most thoroughly described and is hypothesized to be its central function.…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology

et al. 2021

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DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson’s disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1′s role as a plausible novel therapeutic target for cardiovascular disease.

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Section: Introductionmentioning

confidence: 99%

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology

et al. 2021

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“…Several studies reported the requirement of DJ-1 for the maintenance of the transformed phenotype (e.g., uncontrolled proliferation, contact inhibition loss, anchorageindependent growth, extracellular matrix invasion) in cancer cells, as well as for the regulation of transformed growth, survival, chemoresistance, and metastasis formation and differentiation [28][29][30][31][32]. For instance, in the context of transcriptional activity, even though DJ-1 does not bind the DNA, it works as a transcription activator by sequestering inhibitory factors of crucial genes involved in cancer progression including p53, the AR, Nrf2, and PSF [33].…”

Section: Dj-1 In Cancer Signalingmentioning

confidence: 99%

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

Olivo

Chimia

Ceramella

et al. 2022

Cells

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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.

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“…DJ-1/PARK7 is a highly conserved homodimer protein that was initially cloned as a putative oncogene capable of transforming NIH3T3 cells in cooperation with H-Ras [6]. Many studies have shown that DJ-1 is overexpressed in prostate cancer, pancreatic cancer, colon cancer, etc., and is positively correlated with tumor metastasis and negatively correlated with patient survival [7][8][9]. In ESCC, patients with high nuclear expression of DJ-1 have a higher rate of distant metastasis within one year after surgery [10].…”

Section: Introductionmentioning

confidence: 99%

Irradiation induces DJ-1 secretion from esophageal squamous cell carcinoma cells to accelerate metastasis of bystander cells via a TGF-β1 positive feedback loop

Sun

Song

et al. 2022

J Exp Clin Cancer Res

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Background Radiation-induced bystander effect (RIBE) can promote tumor metastasis contributing to the failure of radiotherapy for esophageal squamous cell carcinoma (ESCC). Aberrant expression of DJ-1 has been identified in ESCC; however, the relationship between DJ-1 and RIBE in ESCC remains unknown. Methods We detected DJ-1 in the serum and cell supernatants by enzyme-linked immunosorbent assay (ELISA) and evaluated tumor metastasis by phenotypic experiments in vivo and in vitro. RNA-seq, mass spectrometry, western blot (WB), immunoprecipitation (IP), and dual-luciferase reporter assays were performed to explore the underlying mechanisms. Results DJ-1 was highly expressed in the serum of patients with ESCC receiving radiotherapy and was significantly overexpressed in the medium of ESCC cells receiving irradiation. DJ-1 promoted tumor metastasis via the TGF-β1 pathway. Mechanistic studies revealed that DJ-1 bound to HSC70 to promote Smad3 phosphorylation and nuclear aggregation in a protein-interaction manner, which activated the transcription of Thrombospondin-1 (TSP1). Subsequently, the activation of TGF-β1 by TSP1 re-promoted Smad3 phosphorylation and nuclear aggregation, constituting a positive feedback loop to strengthen the metastasis of ESCC cells, which was effectively blocked by LY2109761 and LSKL. Moreover, higher levels of serum DJ-1 in patients with ESCC were related to a poorer prognosis of radiotherapy. Conclusions Irradiation can induce ESCC cells secreting DJ-1. Secreted DJ-1 enters bystander cells to initiate activation of the TGF-β1 pathway via the DJ-1/HSC70/Smad3 signaling axis. The TSP1/TGF-β1/Smad3 positive feedback pathway constitutes the core pathway that promotes ESCC metastasis. DJ-1 is a useful biomarker for predicting the efficacy of radiotherapy and a potential therapeutic target for reversing RIBE in ESCC. Graphical Abstract Schematic diagram showing the underlying mechanism that irradiation-induced secretion of DJ-1 accelerates the metastasis of bystander ESCC cells.

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Knockdown of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition

Cited by 10 publications

References 19 publications

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology

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

Irradiation induces DJ-1 secretion from esophageal squamous cell carcinoma cells to accelerate metastasis of bystander cells via a TGF-β1 positive feedback loop

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