High expression of PU.1 is associated with Her‑2 and shorter survival in patients with breast cancer

Lin, Jing; Liu, Wei; Luan, Tian; Yuan, Lili; Jiang, Wei; Cai, Huilong; Yuan, Weiguang; Wang, Yuwen; Zhang, Qingyuan; Wang, Lihong

doi:10.3892/ol.2017.7204

Cited by 12 publications

(16 citation statements)

References 32 publications

(34 reference statements)

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“…Both interferon (IFN) regulatory factors IRF8 and IRF4 bind PU.1 cooperatively at the IRF/PU.1 site in RAW264.7 cells [66]. PU.1 promotes macrophage differentiation toward alternatively activated macrophages and is involved in the development of many types of tumors including breast cancer [67], myeloma [68], acute myeloid leukemia [69], glioma [70] and hepatocellular carcinoma [71].…”

Section: Pu1mentioning

confidence: 99%

“…Growing evidence indicates that extracellular accumulation of lactate produced by cancer cells stimulates expression of pro-angiogenic and tumor-promoting factors in TAMs, and consequently induces TAM-mediated immunosuppression [244,245]. The importance of lactate in the activation of tumor-promoting activity of TAMs was demonstrated in co-culture system of human monocytic cell line THP-1 with MDA-MB-231 and MCF-7 human breast cancer cells [67]. Lactate programmed TAM-like phenotype of THP-1 cells (upregulation of CD206 and CD163 expression and elevated production of TGF-b1, IL-10, VEGF) and stimulated the expression and secretion of CCL5.…”

Section: Role Of Lactate and Glycolysismentioning

confidence: 99%

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Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Larionova

Kazakova

Patysheva

et al. 2020

Cancers

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Macrophages are key innate immune cells in the tumor microenvironment (TME) that regulate primary tumor growth, vascularization, metastatic spread and tumor response to various types of therapies. The present review highlights the mechanisms of macrophage programming in tumor microenvironments that act on the transcriptional, epigenetic and metabolic levels. We summarize the latest knowledge on the types of transcriptional factors and epigenetic enzymes that control the direction of macrophage functional polarization and their pro- and anti-tumor activities. We also focus on the major types of metabolic programs of macrophages (glycolysis and fatty acid oxidation), and their interaction with cancer cells and complex TME. We have discussed how the regulation of macrophage polarization on the transcriptional, epigenetic and metabolic levels can be used for the efficient therapeutic manipulation of macrophage functions in cancer.

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Section: Pu1mentioning

confidence: 99%

Section: Role Of Lactate and Glycolysismentioning

confidence: 99%

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Larionova

Kazakova

Patysheva

et al. 2020

Cancers

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“…KDM2B 22,23 and HNF4A 24 are potential therapeutic targets and well-known for their role in cancer progression. The upregulated TFs in MPDAC are known to be involved in shorter survival of cancer patients (PU1 25 ), metastasis (TP63 26 ), vasculogenesis (FLI-1 27 ) and cellular functions including cell proliferation, DNA damage and repair, apoptosis and stress response (FOXO1 28,29 ).…”

Section: Resultsmentioning

confidence: 99%

Systems Biology Approach to Identify Novel Genomic Determinants for Pancreatic Cancer Pathogenesis

Khatri

Ganguly

Sharma

et al. 2019

Sci Rep

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a 5-year survival rate of <8%. Its dismal prognosis stems from inefficient therapeutic modalities owing to the lack of understanding about pancreatic cancer pathogenesis. Considering the molecular complexity and heterogeneity of PDAC, identification of novel molecular contributors involved in PDAC onset and progression using global “omics” analysis will pave the way to improved strategies for disease prevention and therapeutic targeting. Meta-analysis of multiple miRNA microarray datasets containing healthy controls (HC), chronic pancreatitis (CP) and PDAC cases, identified 13 miRNAs involved in the progression of PDAC. These miRNAs showed dysregulation in both tissue as well as blood samples, along with progressive decrease in expression from HC to CP to PDAC. Gene-miRNA interaction analysis further elucidated 5 miRNAs (29a/b, 27a, 130b and 148a) that are significantly downregulated in conjunction with concomitant upregulation of their target genes throughout PDAC progression. Among these, miRNA-29a/b targeted genes were found to be most significantly altered in comparative profiling of HC, CP and PDAC, indicating its involvement in malignant evolution. Further, pathway analysis suggested direct involvement of miRNA-29a/b in downregulating the key pathways associated with PDAC development and metastasis including focal adhesion signaling and extracellular matrix organization. Our systems biology data analysis, in combination with real-time PCR validation indicates direct functional involvement of miRNA-29a in PDAC progression and is a potential prognostic marker and therapeutic candidate for patients with progressive disease.

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“…Зрелые Т-лимфоциты не экспрессируют PU.1. В контексте солидных опухолей изучение прогностической и клинической значимости экспрессии PU.1 проведено для рака молочной железы и глиом [11,12], причем для обеих нозологий показана связь экспрессии маркера с прогрессией и неблагоприятным прогнозом. Учитывая тот факт, что PU.1 продуцируется как макрофагами, так и B-клетками, нами проведено комплексное исследование экспрессии PU.1 + , CD68 + и CD20 + клеток в строме КРР.…”

Section: Discussionunclassified

“…Низкий уровень экспрессии PU.1 ассоциирован с B-клеточной дифференцировкой, в то время как высокий уровень экспрессии данного белка стимулирует развитие макрофагов. Опубликовано всего два исследования, посвященных экспрессии PU.1 в солидных опухолях и ее прогностической значимости [11,12].…”

Section: Introductionunclassified

PU.1 is a nuclear factor of immunocompetent cells of tumor stroma in colorectal cancer

Ковалева¹,

Gratchev²,

Podlesnaya³

et al. 2021

Clin. Exp. Morphology

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Introduction. Tumor-associated macrophages (TAMs) are traditionally considered to be a pro-tumor fac-tor that promotes the growth of various tumors; however, for colorectal carcinomas (CRC), the prognostic significance of TAMs has not been fully determined, which may be due to the lack of macrophage markers suitable for this tumor type. The aim of this work was to study the expression of the nuclear marker of stromal cells PU.1 in colorectal tumors and its association with the clinical and morphological tumor characteristics. Materials and methods. We performed an immunohistochemical analysis to assess the expression of PU.1, CD68, and CD20 in 85 primary CRCs. The Mann-Whitney test was used to determine statistically significant differences in independent groups. Correlation analysis of the expression of the studied protein was carried out by determining the Spearman’s rank correlation coefficient. Differences were considered statistically significant at p <0.05. Results. We analyzed the expression of PU.1, CD68, and CD20 in CRC and detected positive PU.1 and CD68 expressions in tumor stromal cells in all of the studied samples. Expression of CD20 was observed in 87% of cases. We showed that in colorectal tumors all CD68+ or CD20+ cells express PU.1 and that PU.1 and CD20 were significantly associated with the disease stage (p=0.036 and p=0.002) and the presence or absence of regional metastases (p=0.022 and p=0.007). In addition, PU.1 showed a significant correlation with the distant metastases’ presence and tumor localization (p=0.031 and p=0.022). Higher content of PU.1 was typical for colon tumors without metastases. CD20 also showed a significant association with tumor size (p=0.025). No significant correlations with clinical and morphological features were found for CD68. We also demonstrated that the number of PU.1+ cells in tumors significantly positively correlates with CD68 (r=0.231, p=0.036) and CD20 (r=0.267, p=0.015). Conclusion. The results of this study indicate that PU.1 can be considered as an independent marker of a favorable prognosis in CRC patients. Keywords: colorectal cancer, expression, CD20, CD68, PU.1, macrophages, B-cells

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High expression of PU.1 is associated with Her‑2 and shorter survival in patients with breast cancer

Abstract: Abstract. The transcription factor PU

Cited by 12 publications

References 32 publications

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Systems Biology Approach to Identify Novel Genomic Determinants for Pancreatic Cancer Pathogenesis

PU.1 is a nuclear factor of immunocompetent cells of tumor stroma in colorectal cancer

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