Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma

Mkrtichyan, Mikayel; Ghochikyan, Anahit; Movsesyan, Nina; Loukinov, Dmitry; Lobanenkov, Victor; Cribbs, David H.; Laust, Amanda K.; Nelson, Edward L.; Agadjanyan, Michael G.

doi:10.1016/j.cellimm.2011.05.007

Cited by 28 publications

(28 citation statements)

References 55 publications

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“…We found BORIS amplification in 10 of 28 (36%) NSCLC, which strongly correlates with reported rates of 20q13 amplification in lung cancer [26], [41]. In agreement with its oncogenic properties, anti-BORIS vaccination strategies demonstrate an inhibition in tumor growth in breast cancer mouse models [28], [42].…”

Section: Discussionsupporting

confidence: 87%

Dose-Dependent Activation of Putative Oncogene SBSN by BORIS

et al. 2012

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Testis-specific transcription factor BORIS (Brother of the Regulator of Imprinted Sites), a paralog and proposed functional antagonist of the widely expressed CTCF, is abnormally expressed in multiple tumor types and has been implicated in the epigenetic activation of cancer-testis antigens (CTAs). We have reported previously that suprabasin (SBSN), whose expression is restricted to the epidermis, is epigenetically derepressed in lung cancer. In this work, we establish that SBSN is a novel non-CTA target of BORIS epigenetic regulation. With the use of a doxycycline-inducible BORIS expressing vector, we demonstrate that relative BORIS dosage is critical for SBSN activation. At lower concentrations, BORIS induces demethylation of the SBSN CpG island and disruption and activation of chromatin around the SBSN transcription start site (TSS), resulting in a 35-fold increase in SBSN expression in the H358 human lung cancer cell line. Interestingly, increasing BORIS concentrations leads to a subsequent reduction in SBSN expression via chromatin repression. In a similar manner, increase in BORIS concentrations leads to eventual decrease of cell growth and colony formation. This is the first report demonstrating that different amount of BORIS defines its varied effects on the expression of a target gene via chromatin structure reorganization.

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Section: Discussionsupporting

confidence: 87%

Dose-Dependent Activation of Putative Oncogene SBSN by BORIS

et al. 2012

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“…BORIS is required for cell proliferation in certain types of cancer1516171819. In breast cancer, silencing of BORIS by short interfering RNA (siRNA) suppressed cancer cell viability and induced caspase 3/7 activity15.…”

mentioning

confidence: 99%

Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer

Zhang

Fang

Song

et al. 2017

Sci Rep

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Identifying oncogenes that promote cancer cell proliferation or survival is critical for treatment of colorectal cancer. The Brother of Regulator of Imprinted Sites (BORIS) is frequently expressed in most types of cancer, but rarely in normal tissues. Aberrantly expressed BORIS relates to colorectal cancer, but its function in colorectal cancer cells remains unclear. In addition, previous studies indicated the significance of cytoplasm-localized BORIS in cancer cells. However, none of them investigated its function. Herein, we investigated the functions of BORIS in cancer cell proliferation and apoptosis and the role of cytoplasm-localized BORIS in colorectal cancer. BORIS expression correlated with colorectal cancer proliferation. BORIS overexpression promoted colorectal cancer cell growth, whereas BORIS knockdown suppressed cell proliferation. Sensitivity of colorectal cancer cells to 5-fluorouracil (5-FU) was inversely correlated with BORIS expression. These data suggest that BORIS functions as an oncogene in colorectal cancer. BORIS silencing induced reactive oxygen species (ROS) production and apoptosis, whereas BORIS supplementation inhibited apoptosis induced by BORIS short interfering RNA (siRNA), hydrogen peroxide (H2O2) or 5-FU. Introduction of BORIS-ZFdel showed that cytoplasmic localization of BORIS inhibited apoptosis but not ROS production. Our study highlights the anti-apoptotic function of BORIS in colorectal cancer.

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“…Second, it also suggests that Epi-drivers might be targeted by cancer vaccines, as has been suggested for Cancer/Testis antigens [17]. In fact, through a metastatic mammary mouse model, a BORIS-based cancer vaccine delivered by dendritic cells was shown to be effective in inhibiting tumor growth and the formation of metastasis [41]. Clinical trials targeting CT genes are few, but NY-ESO-1 (New York esophageal squamous cell carcinoma 1, also known as CTAGB1, CT6.1) was targeted by adoptive immunotherapy employing genetically modified lymphocytes in patients with metastatic synovial cell sarcoma or melanoma patients and was shown to be effective with impressive responses to treatment with no apparent toxicity effect (Effective responses of 67 % and 45 %) [42].…”

Section: Resultsmentioning

confidence: 99%

Hypomethylation of the CTCFL/BORIS promoter and aberrant expression during endometrial cancer progression suggests a role as an Epi-driver gene

et al. 2014

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Cancers arise through accumulating genetic and epigenetic alterations, considered relevant for phenotype and approaches to targeting new therapies. We investigated a unique collection of endometrial cancer precursor samples and clinically annotated primary and metastatic lesions for two evolutionary and functionally related transcription factors, CCCTC-binding factor (zinc finger protein) (CTCF) and its paralogue CTCF-like factor, also denoted Brother of the Regulator of Imprinted Sites (CTCFL/BORIS). CTCF, a chromatin modeling- and transcription factor, is normally expressed in a ubiquitous fashion, while CTCFL/BORIS is restricted to the testis. In cancer, CTCF is thought to be a tumor suppressor, while CTCFL/BORIS has been suggested as an oncogene. CTCF mutations were identified in 13 %, with CTCF hotspot frameshift mutations at p.T204, all observed solely in the endometrioid subtype, but with no association with outcome. Interestingly, CTCFL/BORIS was amongst the top ranked genes differentially expressed between endometrioid and non-endometrioid tumors, and increasing mRNA level of CTCFL/BORIS was highly significantly associated with poor survival. As aberrant CTCFL/BORIS expression might relate to loss of methylation, we explored methylation status in clinical samples from complex atypical hyperplasia, through primary tumors to metastatic lesions, demonstrating a pattern of DNA methylation loss during disease development and progression in line with the increase in CTCFL/BORIS mRNA expression observed. Thus, CTCF and CTCFL/BORIS are found to diverge in the different subtypes of endometrial cancer, with CTCFL/BORIS activation through demethylation from precursors to metastatic lesions. We thus propose, CTCFL/BORIS as an Epi-driver gene in endometrial cancer, suggesting a potential for future vaccine development.

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Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma

Cited by 28 publications

References 55 publications

Dose-Dependent Activation of Putative Oncogene SBSN by BORIS

Dose-Dependent Activation of Putative Oncogene SBSN by BORIS

Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer

Hypomethylation of the CTCFL/BORIS promoter and aberrant expression during endometrial cancer progression suggests a role as an Epi-driver gene

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