Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors

Mostovich, Lyudmila A.; Prudnikova, Tatiana Y.; Kondratov, Oleksandr; Loginova, D. B.; Vavilov, Pavel V.; Рыкова, В. И.; Сидоров, С. В.; Pavlova, Tatiana V.; Kashuba, Vladimir I.; Zabarovsky, Eugene R.; Grigorieva, Elvira V.

doi:10.4161/cam.5.5.17949

Cited by 41 publications

(28 citation statements)

References 39 publications

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“…Furthermore, Ingenuity pathway analysis (IPA) identified relevant signalling networks activated and up-regulated in DTC tumors compared to mammary tumors (Figure 2B). Despite comparable tumor volume size (data not shown), DTC tumors showed increased levels of hypoxia-regulated genes such as the cytokine VEGF [20], Adm (adrenomedullin) [21], Bnip3 (BCL2/Adenovirus E1B 19kD-Interacting Protein 3) [22], Pfkfb3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3) [23], Itga9 (Integrin alpha-9) [24], and NRG1 (neuregulin 1) [25] (Figure 2B). The mRNA expression of VEGF and BNIP3 was also validated by qPCR.…”

Section: Resultsmentioning

confidence: 99%

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

et al. 2016

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Metastasis is the final stage of cancer progression. Some evidence indicates that tumor cell dissemination occurs early in the natural history of cancer progression. Disseminated tumor cells (DTC) have been described in the bone marrow (BM) of cancer patients as well as in experimental models, where they correlate with later development of metastasis. However, little is known about the tumorigenic features of DTC obtained at different time points along tumor progression. Here, we found that early DTC isolated from BM of 15-17 week-old Her2/neu transgenic (BALB-neuT) mice were not tumorigenic in immunodeficient mice. In contrast, DTC-derived tumors were easily detectable when late DTC obtained from 19-22 week-old BALB-neuT mice were injected. Angiogenesis, which contributes to regulate tumor dormancy, appeared dispensable to reactivate late DTC, although it accelerated growth of secondary DTC tumors. Compared with parental mammary tumors, gene expression profiling disclosed a distinctive transcriptional signature of late DTC tumors which was enriched for hypoxia-related transcripts and was maintained in ex-vivo cell culture. Altogether, these findings highlight a different tumorigenic potential of early and late DTC in the BALB-neuT model and describe a HIF-1α-related transcriptional signature in DTC tumors, which may render DTC angiogenesis-competent, when placed in a favourable environment.

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Section: Resultsmentioning

confidence: 99%

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

et al. 2016

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“…a9 integrin is expressed on various cells including airway epithelial cells and smooth muscle cells (27), as well as cancer cells such as melanoma and breast tumor cells (28,29). The known ligands for a9 integrin are OPN, TN-C, propolypeptide of von Willebrand factor, fibronectin-EIIIA, and polydom (6,7,23,30,31).…”

Section: Discussionmentioning

confidence: 99%

A Novel α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases

Matsumoto

Kawa

Nakatsuru

et al. 2017

The Journal of Immunology

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The integrin α9β1 is a key receptor involved in the development of autoimmune diseases. However, the detailed mechanism for the association of α9β1 integrin with its ligands remains unclear. In this study, we introduce XCL1/lymphotactin, a member of the chemokine family, as a novel ligand for α9 integrin. Using α9 integrin-overexpressing NIH3T3 cells and endogenously α9 integrin-expressing human rhabdomyosarcoma cells, the interaction between XCL1 and α9 integrin was confirmed by pull-down assays. XCL1 enhanced α9 integrin-dependent cell migration of these cells, thus acting on α9 integrin as a chemoattractant. We also analyzed the in vivo function of XCL1 in the development of anti-type II collagen Ab-induced inflammatory arthritis (CAIA) in BALB/c mice and experimental autoimmune encephalomyelitis in C57BL/6 mice, because α9 integrin is involved in these autoimmune disease models. In CAIA, recombinant XCL1 aggravated the disease and this exacerbation was inhibited by an anti-α9 integrin Ab. An XCL1-neutralizing Ab produced in this study also ameliorated CAIA. Furthermore, the XCL1-neutralizing Ab abrogated the disease progression in experimental autoimmune encephalomyelitis. Therefore, to our knowledge this study provides the first in vitro and in vivo evidence that the interaction between XCL1 and α9 integrin has an important role for autoimmune diseases.

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“…Several clinical trials of 5-aza-dC administration conducted in diverse tumor types have shown various degrees of efficacy, particularly in solid tumors (Mostovich et al, 2011). Control of cell cycle progression is considered a potentially effective strategy for tumor growth, and the molecular analysis of common malignancies in humans have revealed that cell cycle regulators are frequently mutated (Kennedy et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Effect of inhibition of MEK pathway on 5-aza-deoxycytidine-suppressed pancreatic cancer cell proliferation

Wang¹,

Wang²,

Jiang³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Pancreatic adenocarcinoma is a lethal disease because it is inoperable at the time of diagnosis. Therefore, the search for new therapeutic approaches is critical. The abnormal expression of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) pathway and alteration in epigenetic modification (DNA methylation and acetylation of histones) is a common feature in the majority of human pancreatic adenocarcinomas. Because DNA methyltransferase levels are regulated by the MEK pathway, we examined the effects of an MEK inhibitor, PD98059, on the action of DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC), the epigenetic agent in the pancreatic cell line CFPAC1. Our results showed that PD98059 significantly potentiated the capability of 5-azadC to induce a cessation of cell proliferation concomitant with cell cycle arrest. We also observed an increase in tumor suppressor gene expression associated with the efficacy of treatment with PD98059 and 5-aza-dC. Further studies explored the molecular mechanisms by which . We found that 5-aza-dC induced acetylation of histone H3 on the p21 WAF1 gene promoter and demethylation status on the p21 WAF1 gene promoter region. These effects were strikingly enhanced by the concomitant blockade of the MEK pathway. Furthermore, knockdown of p21 WAF1 by small interfering RNA rescued human pancreatic cancer cells from 5-aza-dC-mediated growth inhibition. Taken together, our results show that the MEK inhibitor enhanced the effects of 5-aza-dC in human pancreatic cancer cells. These results suggest that the MEK signal pathway may be a potential target for pancreatic cancer therapy.

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Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors

Cited by 41 publications

References 39 publications

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

A Novel α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases

Effect of inhibition of MEK pathway on 5-aza-deoxycytidine-suppressed pancreatic cancer cell proliferation

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