Tumor suppressor p53 down-regulates expression of human leukocyte marker CD43 in non-hematopoietic tumor cells

Kadaja-Saarepuu, Lilian; Lõoke, Marko; Balikova, Anna; Maimets, Toivo

doi:10.3892/ijo.2011.1208

Cited by 5 publications

(6 citation statements)

References 42 publications

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“…CD43 (also known as leukosialin) is a cell surface antigen expressed by most haematopoietic cells that is an important regulator of immune cell function and is involved in regulation of cell adhesion and proliferation 67, 68 . In humans, overexpression of CD43 in non-haematopoietic cells activates the ARF—p53 tumour suppressor pathway [G] and leads to apoptosis 69, 70 . However, p53 specifically downregulates the expression of CD43 at the mRNA and protein level in non-haematopoietic cells, suggesting a negative feedback loop between p53 and CD43 69, 70 .…”

Section: The Role Of P53 In Immunitymentioning

confidence: 99%

“…In humans, overexpression of CD43 in non-haematopoietic cells activates the ARF—p53 tumour suppressor pathway [G] and leads to apoptosis 69, 70 . However, p53 specifically downregulates the expression of CD43 at the mRNA and protein level in non-haematopoietic cells, suggesting a negative feedback loop between p53 and CD43 69, 70 .…”

Section: The Role Of P53 In Immunitymentioning

confidence: 99%

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Emerging roles of p53 and other tumour-suppressor genes in immune regulation

et al. 2016

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Tumour-suppressor genes are indispensable for the maintenance of genomic integrity. Recently, several of these genes, including p53, PTEN, RB1 and ARF, have been implicated in immune responses and inflammatory diseases. In particular, the p53 tumour-suppressor pathway is involved in crucial aspects of tumour immunology and in homeostatic regulation of immune responses. Other studies have identified roles for p53 in various cellular processes, including metabolism and stem cell maintenance. Here, we discuss the emerging roles of p53 and other tumour-suppressor genes in tumour immunology as well as in additional immunological settings, such as virus infection. This relatively unexplored area could yield important insights into the homeostatic control of immune cells in health and disease, and facilitate the development of more effective immunotherapies. Consequently, tumour-suppressor genes are emerging as potential guardians of immune integrity.

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Section: The Role Of P53 In Immunitymentioning

confidence: 99%

Section: The Role Of P53 In Immunitymentioning

confidence: 99%

Emerging roles of p53 and other tumour-suppressor genes in immune regulation

et al. 2016

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“…It is also involved in the progression of triple negative breast cancer cells ( 39 ). CD43 is involved in cell adhesion and migration, and is downregulated by the tumor suppressor p53, suggesting its role in tumorigenesis ( 26 , 30 , 40 ). These findings suggest that downregulation of CSF2RA and CD43 is involved in miR7083-5p-mediated M2 to M1 macrophage reprogramming, and contributes to the inhibition of tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic therapy reprograms M2-type tumor-associated macrophages into an M1-like phenotype by upregulating miR-7083-5p

et al. 2022

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Reprogramming M2-type, pro-tumoral tumor-associated macrophages (TAMs) into M1-type, anti-tumoral macrophages is a key strategy in cancer therapy. In this study, we exploited epigenetic therapy using the DNA methylation inhibitor 5-aza-2’-deoxycytidine (5-aza-dC) and the histone deacetylation inhibitor trichostatin A (TSA), to reprogram M2-type macrophages into an M1-like phenotype. Treatment of M2-type macrophages with the combination of 5-aza-dC and TSA decreased the levels of M2 macrophage cytokines while increasing those of M1 macrophage cytokines, as compared to the use of either therapy alone. Conditioned medium of M2 macrophages treated with the combination of 5-aza-dC and TSA sensitized the tumor cells to paclitaxel. Moreover, treatment with the combination inhibited tumor growth and improved anti-tumor immunity in the tumor microenvironment. Depletion of macrophages reduced the anti-tumor growth activity of the combination therapy. Profiling of miRNAs revealed that the expression of miR-7083-5p was remarkably upregulated in M2 macrophages, following treatment with 5-aza-dC and TSA. Transfection of miR-7083-5p reprogrammed the M2-type macrophages towards an M1-like phenotype, and adoptive transfer of M2 macrophages pre-treated with miR-7083-5p into mice inhibited tumor growth. miR-7083-5p inhibited the expression of colony-stimulating factor 2 receptor alpha and CD43 as candidate targets. These results show that epigenetic therapy upon treatment with the combination of 5-aza-dC and TSA skews M2-type TAMs towards the M1-like phenotype by upregulating miR-7083-5p, which contributes to the inhibition of tumor growth.

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“…CD43 is an important contributor to immune homeostasis and is expressed on most hematopoietic cells. It regulates immune cell adhesion and proliferation [84]. Also, overexpression of CD43 activates the ARF-p53 tumor-suppressor pathway, which can lead to cell death [85].…”

Section: P53 General Influence On Immune Response Pathwaysmentioning

confidence: 99%

Modulation of immune responses by the tumor suppressor p53

Lowe¹,

Shatz²,

Resnick³

et al. 2013

Biodiscovery

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The commonly held view of the tumor suppressor p53 as a regulator of cell proliferation, apoptosis and senescence has expanded greatly in recent years to cover many biological processes as well as external and internal stress responses. Since the discovery over 30 years ago of p53 as a cellular protein that co-precipitates with the large T antigen of Simian Virus SV40, there has been an intertwining of p53 activities with immunerelated processes, especially as relates to cancer. A variety of interactions between the p53 and the immune stress systems are currently being addressed that suggest opportunities to utilize p53 in modulating immunological activities. Here, we discuss those interactions along with implications for human disease.

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Tumor suppressor p53 down-regulates expression of human leukocyte marker CD43 in non-hematopoietic tumor cells

Cited by 5 publications

References 42 publications

Emerging roles of p53 and other tumour-suppressor genes in immune regulation

Emerging roles of p53 and other tumour-suppressor genes in immune regulation

Epigenetic therapy reprograms M2-type tumor-associated macrophages into an M1-like phenotype by upregulating miR-7083-5p

Modulation of immune responses by the tumor suppressor p53

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