ENTPD1 (CD39) Expression Inhibits UVR-Induced DNA Damage Repair through Purinergic Signaling and Is Associated with Metastasis in Human Cutaneous Squamous Cell Carcinoma

Whitley, Melodi Javid; Suwanpradid, Jutamas; Lai, Chester; Jiang, Simon W.; Cook, Jonathan L.; Zelac, Daniel E.; Rudolph, Ross; Corcoran, David L.; Degan, Simone; Spasojević, Ivan; Levinson, Howard; Erdmann, Detlev; Reid, Claire; Zhang, Jennifer; Robson, Simon C.; Healy, Eugene; Havran, Wendy L.; MacLeod, Amanda S.

doi:10.1016/j.jid.2021.02.753

Cited by 12 publications

(8 citation statements)

References 70 publications

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“…The signaling pathways which are related to adenosine pathway were determined and they were interleukin which play an important role in information transmission, activation and regulation of immune cells, immune cells such as T cell activation, T cell receptor, B cell receptor signaling pathways and Tolllike signaling pathways. Many of the related pathways are related to tumor immunity, which indicates that the adenosine pathway affects tumors through the regulation of immune cells such as T cells and B cells, which are consistent with the high expressions of AP related genes in immune cells, such as NT5E and ENTPD1 are abundant expression on T cells [41][42][43]. In the ADO unfavored tumors, the adenosine genes were highly correlated to angiogenesis, matrix remodeling and tumor brosis, and the results suggests that the adenosine pathways can be served as indicator for tumor growth.…”

Section: Discussionsupporting

confidence: 57%

Application of adenosine pathway prediction model in tumor classification and precision cancer medicine

Gao

Chen

et al. 2022

Preprint

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Cancer is a large group of diseases that exert heterogeneity individually, which resulted in the various lifetime individually and the specific response to anti-cancer drugs. Classification of patients as the prognostics is thereafter the key point for drug selection and therapeutic effect. Adenosine pathway which hydrolyzes extracellular ATP into adenosine has been recognized as new immune checkpoint pathway that can significantly impair anti-tumor immunity of multiple types of cancer. Therefore, a prognostic model based on adenosine pathway would benefit for cancer classification and treatment. In this study, 25 adenosine pathway related genes were screened from literature. An adenosine pathway prediction model (AP) based on 9769 patients from TCGA were constructed for cancer classification, and the AP model was sufficient to distinguish the patients with long overall survivals (OS) from short OS. Cancers could be categorized into two types (ADO unfavored and ADO favored) based on AP model. Next, the tumor microenvironment of two subtypes were characterized and they exhibit different cell components and immune patterns. Based on GEO dataset, AP model was capable to screen proper anti-cancer drugs for patients. To identify key genes that cause drug tolerance, the AP related genes and their drug sensitivity network were constructed and a series of key genes and the corresponding drugs were identified. Finally, AP model and drug sensitivity network identified that the expression of NT5E is correlated to the poor survival of patients with APHigh subtype, and the application of NT5E related drugs may be beneficial for the treatment of patients with APHigh subtype.

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Section: Discussionsupporting

confidence: 57%

Application of adenosine pathway prediction model in tumor classification and precision cancer medicine

Gao

Chen

et al. 2022

Preprint

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“…The same study showed that increased expression of the uPAR protein was correlated with the downregulation of hsa-miR-340-5p and hsa-miR-377-3p [ 7 ]. Another protein, ENTPD1, was found to demonstrate significantly higher expression in human cSCC that metastasized compared to tumors that were nonmetastatic ([+] Met, n = 54, [−] Met, n = 51, p < 0.001) [ 61 ]. Finally, poorly differentiated cSCC displayed significantly higher cytoplasmic and lower nuclear iASPP expression compared to well-differentiated tumors [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular Alterations in Cutaneous Squamous Cell Carcinoma in Immunocompetent and Immunosuppressed Hosts—A Systematic Review

Tsang

Tam

2023

Cancers

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The characterization of cutaneous squamous cell carcinoma (cSCC) at the molecular level is lacking in the current literature due to the high mutational burden of this disease. Immunosuppressed patients afflicted with cSCC experience considerable morbidity and mortality. In this article, we review the molecular profile of cSCC among the immunosuppressed and immunocompetent populations at the genetic, epigenetic, transcriptomic, and proteometabolomic levels, as well as describing key differences in the tumor immune microenvironment between these two populations. We feature novel biomarkers from the recent literature which may serve as potential targets for therapy.

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“…For example, several works have been reviewed to present a link between increased NK cell infiltration or activation and B2m-deficient tumors [ 45 ]. The increased level of the enzyme encoded by Entpd1 (also known as CD39), which catalyzes the rate-limiting step of the conversion of extracellular ATP to adenosine in the tumor microenvironment, has been associated with metastasis [ 50 ]. A recent work has confirmed that CD39+ regulatory T cells (Tregs) were strongly involved in immunosuppression through the HIF-1-induced-upregulation of CD39 in hepatocellular carcinoma cells, which generated extracellular adenosine (eADO) stimulating the accumulation of immunosuppressive plasmacytoid dendritic cells [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma

Pouliquen

Malloci

Boissard

et al. 2022

IJMS

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Curcumin exhibits both immunomodulatory properties and anticarcinogenic effects which have been investigated in different experimental tumor models and cancer types. Its interactions with multiple signaling pathways have been documented through proteomic studies on malignant cells in culture; however, in vivo approaches are scarce. In this study, we used a rat model of highly invasive peritoneal mesothelioma to analyze the residual tumor proteomes of curcumin-treated rats in comparison with untreated tumor-bearing rats (G1) and provide insights into the modifications in the tumor microenvironment/malignant cell crosstalk. The cross-comparing analyses of the histological sections of residual tumors from two groups of rats given curcumin twice on days 21 and 26 after the tumor challenge (G2) or four times on days 7, 9, 11 and 14 (G3), in comparison with G1, identified a common increase in caveolin-1 which linked with significant abundance changes affecting 115 other proteins. The comparison of G3 vs. G2 revealed additional features for 65 main proteins, including an increase in histidine-rich glycoprotein and highly significant abundance changes for 22 other proteins regulating the tumor microenvironment, linked with the presence of numerous activated T cells. These results highlight new features in the multiple actions of curcumin on tumor microenvironment components and cancer cell invasiveness.

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ENTPD1 (CD39) Expression Inhibits UVR-Induced DNA Damage Repair through Purinergic Signaling and Is Associated with Metastasis in Human Cutaneous Squamous Cell Carcinoma

Cited by 12 publications

References 70 publications

Application of adenosine pathway prediction model in tumor classification and precision cancer medicine

Application of adenosine pathway prediction model in tumor classification and precision cancer medicine

Molecular Alterations in Cutaneous Squamous Cell Carcinoma in Immunocompetent and Immunosuppressed Hosts—A Systematic Review

Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma

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