CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions

Liao, Shan; Xiao, Songshu; Chen, Hongxiang; Zhang, Manying; Chen, Zhifang; Long, Yuehua; Gao, Lu; Zhu, Guangchao; He, Junyu; Peng, Shuping; Wang, Xiong; Zeng, Zhaoyang; Li, Zheng; Zhou, Ming; Li, Xiaoling; Ma, Jian; Wu, Minghua; Xiang, Juanjuan; Li, Guiyuan; Zhou, Yanhong

doi:10.1002/mc.22677

Cited by 26 publications

(25 citation statements)

References 48 publications

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“…Similar work was completed in cervical cancer, which found CD38 RNA and protein expression to be high in cancerous tissue in the cervix when compared to normal tissue [78]. Follow-up studies from this group determined a distinct growth advantage of cervical cancer cells in in vitro proliferative analyses, as well as in a nude mouse model of cervical tumor growth [79]. The likely mechanism for the regulation of cell proliferation and survival is the prevention of mitochondrial apoptosis through a lack of intracellular calcium stores with CD38 overexpression, as well as downregulation of p53 signaling.…”

Section: Solid Tumorsmentioning

confidence: 74%

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

Konen

Fradette

Gibbons

2019

Cells

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The regulation of the immune microenvironment within solid tumors has received increasing attention with the development and clinical success of immune checkpoint blockade therapies, such as those that target the PD-1/PD-L1 axis. The metabolic microenvironment within solid tumors has proven to be an important regulator of both the natural suppression of immune cell functionality and the de novo or acquired resistance to immunotherapy. Enzymatic proteins that generate immunosuppressive metabolites like adenosine are thus attractive targets to couple with immunotherapies to improve clinical efficacy. CD38 is one such enzyme. While the role of CD38 in hematological malignancies has been extensively studied, the impact of CD38 expression within solid tumors is largely unknown, though most current data indicate an immunosuppressive role for CD38. However, CD38 is far from a simple enzyme, and there are several remaining questions that require further study. To effectively treat solid tumors, we must learn as much about this multifaceted protein as possible—i.e., which infiltrating immune cell types express CD38 for functional activities, the most effective CD38 inhibitor(s) to employ, and the influence of other similarly functioning enzymes that may also contribute towards an immunosuppressive microenvironment. Gathering knowledge such as this will allow for intelligent targeting of CD38, the reinvigoration of immune functionality and, ultimately, tumor elimination.

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Section: Solid Tumorsmentioning

confidence: 74%

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

Konen

Fradette

Gibbons

2019

Cells

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“…The role of CD38 in cell proliferation and apoptosis differs between diseases. Liao et al found that CD38 can promote proliferation and inhibit apoptosis in cervical cancer cells [52]. In CLL cells, CD38/CD31 interactions enhance cell proliferation and migration by activating various genetic pathways [22].…”

Section: Discussionmentioning

confidence: 99%

CD4+CD38+ central memory T cells contribute to HIV persistence in HIV-infected individuals on long-term ART

Song

Zhang

et al. 2020

J Transl Med

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Background: Despite the effective antiretroviral treatment (ART) of HIV-infected individuals, HIV persists in a small pool. Central memory CD4 + T cells (Tcm) make a major contribution to HIV persistence. We found that unlike HLA-DR, CD38 is highly expressed on the Tcm of HIV-infected subjects receiving ART for > 5 years. It has been reported that the half-life of total and episomal HIV DNA in the CD4 + CD38 + T cell subset, exhibits lower decay rates at 12 weeks of ART. Whether CD38 contributes to HIV latency in HIV-infected individuals receiving long-term ART is yet to be addressed. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of HIV-infected subjects receiving suppressive ART. The immunophenotyping, proliferation and apoptosis of CD4 + T cell subpopulations were detected by flow cytometry, and the level of CD38 mRNA and total HIV DNA were measured using real-time PCR and digital droplet PCR, respectively. A negative binomial regression model was used to determine the correlation between CD4 + CD38 + Tcm and total HIV DNA in CD4 + T cells. Results: CD38 was highly expressed on CD4 + Tcm cells from HIV infected individuals on long-term ART. Comparing with HLA-DR − Tcm and CD4 + HLA-DR + T cells, CD4 + CD38 + Tcm cells displayed lower levels of activation (CD25 and CD69) and higher levels of CD127 expression. The proportion of CD38 + Tcm, but not CD38 − Tcm cells can predict the total HIV DNA in the CD4 + T cells and the CD38 + Tcm subset harbored higher total HIV DNA copy numbers than the CD38 − Tcm subset. After transfected with CD38 si-RNA in CD4 + T cells, the proliferation of CD4 + T cells was inhibited. Conclusion: The current date indicates that CD4 + CD38 + Tcm cells contribute to HIV persistence in HIV-infected individuals on long-term ART. Our study provides a potential target to resolve HIV persistence.

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“…Recent studies indicated the role of CD38 in tumorigenesis. For example, CD38 promotes cervical cancer cell growth through reducing ROS levels and inhibiting apoptosis (Liao et al, 2017), and loss of CD38 in human lung adenocarcinoma cells inhibited cell growth, invasion, and xenograft growth in nude mice (Bu et al, 2017). CD38 also augments immunosuppression in cancer by inhibiting CD8 + T function Feng et al, 2017).…”

Section: Cd38-cd38mentioning

confidence: 99%

Subcellular compartmentalization of NAD+ and its role in cancer: A sereNADe of metabolic melodies

Zhu

Liu

Park

et al. 2019

Pharmacology & Therapeutics

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Nicotinamide adenine dinucleotide (NAD +) is an essential biomolecule involved in many critical processes. Its role as both a driver of energy production and a signaling molecule underscores its importance in health and disease. NAD + signaling impacts multiple processes that are dysregulated in cancer, including DNA repair, cell proliferation, differentiation, redoxregulation, and oxidative stress. Distribution of NAD + is highly compartmentalized, with each subcellular NAD + pool differentially regulated and preferentially involved in distinct NAD +-dependent signaling or metabolic events. Emerging evidence suggests that targeting NAD + metabolism is likely to repress many specific mechanisms underlying tumor development and progression, including proliferation, survival, metabolic adaptations, invasive capabilities, heterotypic interactions with the tumor microenvironment, and stress response including notably DNA maintenance and repair. Here we provide a comprehensive overview of how compartmentalized NAD + metabolism in mitochondria, nucleus, cytosol, and extracellular space impacts cancer formation and progression, along with a discussion of the therapeutic potential of NAD +-targeting drugs in cancer.

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CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions

Cited by 26 publications

References 48 publications

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

CD4+CD38+ central memory T cells contribute to HIV persistence in HIV-infected individuals on long-term ART

Subcellular compartmentalization of NAD+ and its role in cancer: A sereNADe of metabolic melodies

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