Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion

Sciortino, Marianna; Camacho-Leal, Maria del Pilar; Orso, Francesca; Grassi, Elena; Costamagna, Andrea; Provero, Paolo; Turco, Emilia; Defilippi, Paola; Taverna, Daniela; Cabodi, Sara

doi:10.1038/s41598-017-01332-z

Cited by 21 publications

(23 citation statements)

References 48 publications

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“…Blimp1 is a transcriptional repressor that controls gene expression changes in B-cell-to-plasmablast transition, which led to silences of B-cell gene expression in PC ( 59 ). High Blimp1 expression tends to trigger BC cell invasion and metastasis formation ( 60 ). Thus, targeting B-cell transcriptional regulators may further influence BC progression and invasiveness, which reinforces the potential of B cells as a promising therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical Impacts and Regulatory Mechanisms

2018

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Currently, tumor-infiltrating B lymphocytes have been recognized as a new hallmark of breast cancer (BC). The function seems to be controversial, either with positive, negative, or no significance in BC’s prediction and prognosis. Moreover, B-cell infiltrates regulate tumor process through productions of antibodies and interleukin-10. The interactions with other lymphocytes and programmed death-1/PD-1 ligand axis are also documented. The regulatory mechanisms will eventually be incorporated into diagnostic and therapeutic algorithms, thus give guide to clinical treatment. In this review, we give new insights into clinical impacts and regulatory mechanisms of tumor-infiltrating B cells, which heralds a new era in immuno-oncology in BC treatment.

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Section: Discussionmentioning

confidence: 99%

New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical Impacts and Regulatory Mechanisms

2018

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“…impair tumor invasiveness in vitro and lung metastasis formation in vivo [39]. In addition, PRDM1 expression positively correlates with a higher probability of developing multiple metastasis in patients with high p130Cas, supporting the major role played by p130Cas in Blimp1-mediated invasion [39].…”

Section: Introductionmentioning

confidence: 94%

“…Interestingly, a later study demonstrated that PRDM1/BLIMP1 played an essential role in transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) signature and cell migration of breast cancer cells via BMP-5 repression ( Figure 1B) [38]. Additionally, both in vitro and in vivo models have recently described the role of PRDM1/Blimp1 in p130Cas/ErbB2 breast cancer invasion; particularly, Blimp1 was highly expressed during p130Cas/ErbB2 dependent invasion in breast cancer cells and the downregulation of its expression was sufficient to severely impair tumor invasiveness in vitro and lung metastasis formation in vivo [39]. In addition, PRDM1 expression positively correlates with a higher probability of developing multiple metastasis in patients with high p130Cas, supporting the major role played by p130Cas in Blimp1-mediated invasion [39].…”

Section: Introductionmentioning

confidence: 95%

“…Additionally, this study showed that Blimp1 expression was negatively regulated by mir-23b, suggesting a role as a tumor suppressor for this miRNA in p130Cas/ErbB2 cells. Altogether, the miR-23b impairment and the ErbB2/p130Cas/MAPK axis activation could increase PRDM1/Blimp1 expression level, thus mediating cell invasion ( Figure 1C) [39].…”

Section: Introductionmentioning

confidence: 96%

“…Additionally, both in vitro and in vivo models have recently described the role of PRDM1/Blimp1 in p130Cas/ErbB2 breast cancer invasion; particularly, Blimp1 was highly expressed during p130Cas/ErbB2 dependent invasion in breast cancer cells and the downregulation of its expression was sufficient to severely impair tumor invasiveness in vitro and lung metastasis formation in vivo [39]. In addition, PRDM1 expression positively correlates with a higher probability of developing multiple metastasis in patients with high p130Cas, supporting the major role played by p130Cas in Blimp1-mediated invasion [39]. Additionally, this study showed that Blimp1 expression was negatively regulated by mir-23b, suggesting a role as a tumor suppressor for this miRNA in p130Cas/ErbB2 cells.…”

Section: Introductionmentioning

confidence: 99%

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Multifaceted Role of PRDM Proteins in Human Cancer

Casamassimi

Rienzo

Zazzo

et al. 2020

IJMS

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The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.

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Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer

Saleh

Taha

Toor

et al. 2020

Cancer Immunol Immunother

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Despite recent advances in colorectal cancer (CRC) treatment, a large proportion of patients show limited responses to therapies, especially in advanced stages. There is an urgent need to identify prognostic biomarkers and/or therapeutic targets in advanced stages, aiming to improve the efficacy of current treatments. We aimed to determine prognostic biomarkers in tumor tissue and circulation of CRC patients, with a special focus on T cell exhaustion markers. We found that mRNA levels of PD-1, TIM-3, CTLA-4, TIGIT, CD160, CD244, KLRG1, TOX2, TOX3, Ki-67, and PRDM1 were elevated in CRC tumor tissues. We also investigated differences in gene expression between early and advanced disease stages. We found that TOX and potentially TIM-3, CTLA-4, VISTA, TIGIT, KLRG1, TOX2, SIRT1, Ki-67, and Helios mRNA levels in tumor tissue were elevated in advanced disease stages, suggesting their potential roles in CRC progression. In contrast, PD-1 and CD160 levels in tumor tissue were downregulated in advanced stages. In the circulation of CRC patients, mRNA levels of PD-1, VISTA and LAG-3 were higher than those of healthy individuals. Moreover, in circulation, PD-1, CTLA-4 and TIGIT mRNA levels were reduced in advanced stages. Interestingly, levels of PD-1 in both tumor tissue and circulation were reduced in advanced stages, suggesting that targeting PD-1 in patients with advanced stages could be less effective. Altogether, these findings suggest some potential T cell exhaustion markers that could be utilized as prognostic biomarkers and/or therapeutic targets for CRC. However, further investigations and validations in larger cohorts are required to confirm these findings.

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Dysregulation of Blimp1 transcriptional repressor unleashes p130Cas/ErbB2 breast cancer invasion

Cited by 21 publications

References 48 publications

New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical Impacts and Regulatory Mechanisms

New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical Impacts and Regulatory Mechanisms

Multifaceted Role of PRDM Proteins in Human Cancer

Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer

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