Targeting the purinergic pathway in breast cancer and its therapeutic applications

Araújo, Julia Beatrice de; Kerkhoff, Vanessa Vitória; Maciel, Sarah Franco Vieira de Oliveira; Silva, Débora Tavares de Resende e

doi:10.1007/s11302-020-09760-9

Cited by 17 publications

(13 citation statements)

References 220 publications

(353 reference statements)

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“…The CD39 /CD73/A2AR signaling pathway has been shown to be associated with poor cancer prognosis. In addition, CD39 and CD73 are also involved in the formation of new lymphatic vessels around tumors and progression of malignant tumors such as breast carcinoma, multiforme glioblastoma and chronic lymphocytic leukemia [ 78 – 80 ]. Importantly, the blockade of adenosine/A2AR pathway resulted in the enhancement of cancer chemotherapy and immunotherapy in numerous cancer types including lung adenocarcinoma, renal clear cell carcinoma, pheochromocytoma and paraganglioma [ 43 , 81 – 83 ].…”

Section: The Expression and Function Of Cd39/cd73/a2ar In Various Can...mentioning

confidence: 99%

CD39/CD73/A2AR pathway and cancer immunotherapy

Xia

Yin

et al. 2023

Mol Cancer

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Cancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases CD39 and CD73 play critical roles in reshaping an immunosuppressive TME. The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors (A1R, A2AR, A2BR and A3R). The A2AR elicits its profound immunosuppressive function via regulating cAMP signaling. The increasing evidence suggests that CD39, CD73 and A2AR could be used as novel therapeutic targets for manipulating the antitumor immunity. In recent years, monoclonal antibodies or small molecule inhibitors targeting the CD39/CD73/A2AR pathway have been investigated in clinical trials as single agents or in combination with anti-PD-1/PD-L1 therapies. In this review, we provide an updated summary about the pathophysiological function of the adenosinergic pathway in cancer development, metastasis and drug resistance. The targeting of one or more components of the adenosinergic pathway for cancer therapy and circumvention of immunotherapy resistance are also discussed. Emerging biomarkers that may be used to guide the selection of CD39/CD73/A2AR-targeting treatment strategies for individual cancer patients is also deliberated.

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Section: The Expression and Function Of Cd39/cd73/a2ar In Various Can...mentioning

confidence: 99%

CD39/CD73/A2AR pathway and cancer immunotherapy

Xia

Yin

et al. 2023

Mol Cancer

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“…As one of the P1 receptors, ADORA2A is involved in the proliferation and invasion of breast cancer [15]. Adenosine Interaction with ADORA2A Promotes Gastric Cancer Metastasis [16].…”

Section: Discussionmentioning

confidence: 99%

ADORA2A promotes proliferation and inhibits apoptosis through PI3K/AKT pathway activation in colorectal carcinoma

Ran

Mou

Peng

et al. 2022

Preprint

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Background：The third most often diagnosed disease globally and the second most prevalent cause of cancer-related death is colorectal cancer (CRC). Numerous human malignancies have been identified to overexpress ADORA2A. However, it is still ambiguous about its function in CRC. Methods: RNA-seq with stable transfected SETDB1 knockdown cells was used to identify the differentially expressed genes. Further, knockdown of ADORA2A in CRC cell lines SW620 and HCT116 were performed with siRNA and overexpression of ADORA2A in SW480 cells were conducted with plasmid. CCK8, colony formation, wound healing and transwell assay were used to detect the effects of cell proliferation, migration and invasion after knockdown and overexpression of ADORA2A. Also, apoptosis was analyzed by flow cytometry, apoptosis-related proteins and key PI3K/AKT pathway proteins were detected using western blotting. Results: ADORA2A was obtained with RNA-seq and played an important role in CRC prognosis. ADORA2A was relatively high expressed in SW620 and HCT116 cell lines compared to SW480 cell line. Knockdown of ADORA2A in SW620 and HCT116 cell lines inhibited cell proliferation, migration and invasion while overexpression of ADORA2A had the opposite results. In addition, ADORA2A also impacted the expression of apoptosis-related proteins, including as Bcl-2, Bax, caspase3 and caspase9, and reduced apoptosis. Furthermore, this process may include the PI3K/AKT signal pathway. Conclusion: ADORA2A promotes CRC progression by PI3K/AKT signaling pathway. It might contribute to management and treatment of CRC.

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“…It still needs to be further explored. In breast cancer, it was reported that P2X7 has a dual function in some cancer, for example, when activated for a short time, P2X7 promotes metastasis, but when activated for long periods, it is related to breast cancer cell death [ 40 ]. The dual function of P2X7 in different stages of tumor is led by fine-tuning regulation of multiple miRNAs.…”

Section: Purinergic Signalling Modulated By Mirnas In Cancersmentioning

confidence: 99%

MicroRNA: Crucial modulator in purinergic signalling involved diseases

Guo

Yang

et al. 2022

Purinergic Signalling

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Both microRNAs (miRNAs) and purinergic signalling are widely and respectively expressed in various tissues of different organisms and play vital roles in a variety of physiological and pathological processes. Here, we reviewed the current publications contributed to the relationship of miRNAs and purinergic signalling in cardiovascular diseases, gastrointestinal diseases, neurological diseases, and ophthalmic diseases. We tried to decode the miRNAs-purinergic signalling network of purinergic signalling involved diseases. The evidence indicated that more than 30 miRNAs (miR-22, miR-30, miR-146, miR-150, miR-155, miR-187, etc.) directly or indirectly modulate P1 receptors (A1, A2A, A2B, A3), P2 receptors (P2X1, P2X3, P2X4, P2X7, P2Y2, P2Y6, P2Y12), and ecto-enzymes (CD39, CD73, ADA2); P2X7 and CD73 could be modulated by multiple miRNAs (P2X7: miR-21, miR-22, miR-30, miR-135a, miR-150, miR-186, miR-187, miR-216b; CD73: miR-141, miR-101, miR-193b, miR-340, miR-187, miR-30, miR-422a); miR-187 would be the common miRNA to modulate P2X7 and CD73.

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Targeting the purinergic pathway in breast cancer and its therapeutic applications

Cited by 17 publications

References 220 publications

CD39/CD73/A2AR pathway and cancer immunotherapy

CD39/CD73/A2AR pathway and cancer immunotherapy

ADORA2A promotes proliferation and inhibits apoptosis through PI3K/AKT pathway activation in colorectal carcinoma

MicroRNA: Crucial modulator in purinergic signalling involved diseases

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