Oncoscience最新文献

{"title":"Nucleostemin: New Stabilizer of ARF","authors":"Bo Cao, Hua Lu","doi":"10.18632/ONCOSCIENCE.282","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.282","url":null,"abstract":"As an essential nucleolar protein for ribosomal assembly and protein production, nucleolar GTPase nucleostemin (NS) is often highly expressed in actively proliferative cells, including stem cells and cancer cells, and therefore thought to play an oncogenic role in various types of human cancers [1]. However, given the heterogeneity of cancer cells, imbalanced expression of NS could trigger distinct events to regulate cell proliferation in different genetic backgrounds. For instance, in wild type p53-harboring osteosarcoma cell line U2OS, increased expression of NS inhibits MDM2 E3 ligase activity toward p53 and thus activates p53, resulting in G1 cell cycle arrest, while knocking down NS also activates p53 indirectly by causing ribosomal stress that induces the interaction of ribosomal protein L5 and L11 with MDM2 and consequently inhibits MDM2 activity toward p53 [2, 3]. \u0000 \u0000Making this NS-engaged regulation more complicated is our recent identification of the alternative reading frame (ARF), an upstream p53 activator in response to oncogenic stress [4], as another NS-binding protein through affinity purification coupled with mass spectrometry [5]. This binding occurs at the N-termini of both NS (amino acid 1–268) and ARF (amino acid 1–65) [5]. Interestingly, although these sites are also required for binding to nucleophosmin (NPM), which was previously shown to prevent ARF from proteosomal degradation by sequestering ARF in the nucleolus [6], NPM and NS do not appear to compete with each other for ARF binding [5]. Instead, NPM and NS are highly likely to form a stable complex with ARF in the nucleolus, working together to protect ARF [5]. However, our data further revealed that NS is not required for NPM to keep ARF in the nucleolus, but responsible for stabilization of nucleoplasmic ARF dissociated from the ARF-NPM complex resulting from depletion of NPM [5]. These findings indicate that abnormal expression of NS, in addition to causing oncogenic effects under certain circumstances and inducing p53 as an counteraction, could also stabilize tumor-suppressor ARF by enhancing the binding of NPM to ARF in the nucleolus and/or by directly interacting with ARF in the nucleoplasm when NPM is absent, providing an alternative surveillance to prevent aberrantly expressed NS-mediated tumor cell proliferation and transformation (Fig. ​(Fig.11). \u0000 \u0000 \u0000 \u0000Figure 1 \u0000 \u0000Nucleostemin regulation of pathways involved in cell cycle arrest and apoptosis \u0000 \u0000 \u0000 \u0000More interestingly, similar to NPM [6], NS is able to bind to ULF and inhibit its E3 ligase activity toward ARF [5], as ULF was identified as an E3 ligase responsible for ARF polyubiquitination and proteosomal degradation in the nucleoplasm, which was inhibited by NPM [6]. Different from NPM, the NS inhibition of ULF appears to occur in the nucleoplasm [5], as NS reduces the interaction between ARF and ULF, inhibiting ULF-mediated ARF polyubiqutination and degradation (Fig. ​(Fig.1).1). Consequently, enforced ex","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"8 1","pages":"940 - 941"},"PeriodicalIF":0.0,"publicationDate":"2015-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90149104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEF2C and SOCS2 in stemness regulation","authors":"C. Vitali, C. Tripodo, M. Colombo","doi":"10.18632/ONCOSCIENCE.279","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.279","url":null,"abstract":"The physiologic stemness of hematopoietic stem cells (HSC) relies on mechanisms constitutively active under steady state and is fundamental to maintain a lifelong HSC reservoir. On the other side, similar stemness features sustained by partially overlapping molecular circuits, which have recently come into focus, confer aggressive aggressiveness in leukemia clones. \u0000 \u0000Suppressor of Cytokine Signalling 2 (SOCS2) belongs to the SOCS family, comprising eight members (SOCS1–7 and CIS) with similar structures, which are induced upon JAK/STAT activation and function as negative regulators. Recent evidences have demonstrated that SOCS2 is endowed with immunological functions in differentiated cells but no apparent functions were identified in HSC despite its expression in steady state condition. \u0000 \u0000Combining analysis of human HSC malignancies and studies on murine HSC under steady state and stress conditions [1], we have recently identified a dual involvement of SOCS2 in the regulation of HSC functions in different contexts and demonstrated a novel regulatory mechanism for SOCS2 expression in HSC. \u0000 \u0000In mice under hematopoietic stress conditions, such as after 5-Fluorouracil-induced myeloablation, hematopoietic cytokines are rapidly produced to sustain bone marrow (BM) recovery. This event induces activation of the JAK-STAT5 pathway consequently upregulating SOCS2. Such negative feedback loop avoids excessive HSC proliferation and eventually the exhaustion of HSC functions. \u0000 \u0000This regulatory function of SOCS2 is completely novel, while the JAK-STAT dependency for its expression is common to the regulatory loop involving other SOCS proteins as well as SOCS2 in other contexts [2]. \u0000 \u0000Also, we uncovered SOCS2 involvement in hematopoietic malignancies. High SOCS2 expression characterized the BM of chronic myeloid leukemia (CML) patients and increased along clone progression toward blast crisis. The highest and widespread SOCS2 expression in BM hematopoietic populations was associated with aggressive acute leukemia subsets, namely acute myeloid (AML) and lymphoblastic leukemias (ALL) with MLL rearrangments and BCR/ABL abnormalities. In AML patients, high SOCS2 was significatively associated with poor prognosis. \u0000 \u0000In AML and ALL patients, high SOCS2 expression also positively correlated with a list of genes that significanly overlapped with leukemic stemness gene signatures [3], suggesting that SOCS2 and hematopoietic stemness can be associated in the context of hematopietic malignancies. Normal HSC and leukemic stem cells (LSC) share some common molecular programs and, conceivably, similar molecular mechanisms could regulate SOCS2 in these populations. \u0000 \u0000Our analysis of public gene expression profiles of AML and ALL excluded that SOCS2 expression could be ascribed only to JAK-STAT pathways activation and suggests that alternative STAT-independent molecular programs should be involved. To our knowledge, this is the first indication of STAT-independent regu","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"31 1","pages":"936 - 937"},"PeriodicalIF":0.0,"publicationDate":"2015-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77602728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mouse models of radiation-induced glioblastoma","authors":"B. Mukherjee, P. Todorova, S. Burma","doi":"10.18632/ONCOSCIENCE.278","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.278","url":null,"abstract":"Glioblastomas (GBM) are lethal brain tumors that can be triggered by exposure to ionizing radiation (IR), even at low doses from CT scans [1]. High doses of IR are also used to treat GBM, but the irradiated tumors inevitably recur. This raises the possibility that genomic changes induced by radiation may contribute not only to glioma initiation, but also to tumor recurrence. Thus, there is a compelling need for experimental model systems that recapitulate the process of radiation-induced gliomagenesis. Such models could not only help predict GBM-development risks from radiation exposure, but also help identify genetic alterations defining radiation-induced GBM, thereby facilitating the development of rational therapies for treating these recalcitrant tumors. \u0000 \u0000Our study published in the journal Oncogene employed a systematic approach to develop sensitive mouse models that can be used to study radiation-induced gliomagenesis [2]. Ink4a, Ink4b and Arf are key tumor suppressor genes that are deleted in a majority of GBMs [3]. We utilized transgenic mice with brain-restricted deletions of these tumor suppressors, individually and in combination, and examined their susceptibility to IR-induced GBM development. The most deleterious lesion inflicted by IR is the DNA double-strand break (DSB). We have shown previously that accelerated ions (particle radiation) induce complex DSBs that are refractory to repair unlike the simple breaks induced by X-rays (electromagnetic radiation) which are repaired to completion [4]. Therefore, we intra-cranially irradiated these transgenic mice with either X-rays or accelerated Fe ions to understand the process of radiation-induced gliomagenesis, and how this may be influenced by DNA damage complexity. We found that these mice did not develop gliomas spontaneously, but were prone to GBM development after exposure to a single, moderate dose of radiation. Remarkably, we found that Fe ions were at least four-fold more effective than X-rays in inducing these tumors, thereby confirming that complex DSBs triggered by accelerated ions are more harmful than simpler breaks induced by X-rays. This finding has important implications as the use of particle radiation (such as protons and carbon ions) for cancer therapy is steadily increasing. Our work indicates that particle radiation could indeed turn out to be more effective than X-rays for tumor control, but this also raises the specter of increased likelihood of secondary cancers triggered by such radiation. \u0000 \u0000Interestingly, while wild type mice did not develop gliomas upon radiation exposure, loss of Ink4a and Arf was sufficient to render these mice susceptible to IR-induced gliomas; additional loss of Ink4b significantly increased tumor incidence. These observations indicate that Ink4a, Ink4b and Arf act as key barriers to radiation-induced gliomagenesis, and confirms previous results from our laboratory and others implicating Ink4b as an important “backup” tumor suppressor f","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"24 1","pages":"934 - 935"},"PeriodicalIF":0.0,"publicationDate":"2015-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77910257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-stimulated microbubble enhancement of radiation treatments: endothelial cell function and mechanism","authors":"A. Al-Mahrouki, Emily Wong, G. Czarnota","doi":"10.18632/ONCOSCIENCE.277","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.277","url":null,"abstract":"Endothelial cell death caused by novel microbubble-enhanced ultrasound cancer therapy leads to secondary tumour cell death. In order to characterize and optimize these treatments, the molecular mechanisms resulting from the interaction with endothelial cells were investigated here. Endothelial cells (HUVEC) were treated with ultrasound-stimulated microbubbles (US/MB), radiation (XRT), or a combination of US/MB+XRT. Effects on cells were evaluated at 0, 3, 6, and 24 hours after treatment. Experiments took place in the presence of modulators of sphingolipid-based signalling including ceramide, fumonisin B1, monensin, and sphingosine-1-phosphate. Experimental outcomes were evaluated using histology, TUNEL, clonogenic survival methods, immuno-fluorescence, electron microscopy, and endothelial cell blood-vessel-like tube forming assays. Fewer cells survived after treatment using US/MB+XRT compared to either the control or XRT. The functional ability to form tubes was only reduced in the US/ MB+XRT condition in the control, the ceramide, and the sphingosine-1-phosphate treated groups. The combined treatment had no effect on tube forming ability in either the fumonisin B1 or in the monensin exposed groups, since both interfere with ceramide production at different cellular sites. In summary, experimental results supported the role of ceramide signalling as a key element in cell death initiation with treatments using US/MB+XRT to target endothelial cells.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"30 1","pages":"944 - 957"},"PeriodicalIF":0.0,"publicationDate":"2015-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76023593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of new miRNA biomarkers associated with HER2-positive breast cancers","authors":"Hossam Tashkandi, N. Shah, Y. Patel, Hexin Chen","doi":"10.18632/ONCOSCIENCE.275","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.275","url":null,"abstract":"Human epidermal growth factor receptor 2 (HER2) is overexpressed/amplified in ∼30% breast cancers which are associated with poor prognosis. microRNAs are small non-coding RNA which play an important role in many physiological conditions including cancer. Here we screened and identified many miRNAs which are dysregulated by HER2 overexpression. In line with our quantitative PCR analysis data, in silico analysis of microRNA expression profiles of 1302 breast tumors revealed that miR-146a-5p is up-regulated and miR-181d and miR-195-5p are down-regulated in HER2-positive tumors. Furthermore, the expression levels of these microRNAs can significantly predict patient survival and thus potentially serve as new prognostic markers for HER2-positive breast cancer.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"15 1","pages":"924 - 929"},"PeriodicalIF":0.0,"publicationDate":"2015-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84979991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT3 and mTOR: co-operating to drive HIF and angiogenesis","authors":"K. Dodd, A. Tee","doi":"10.18632/ONCOSCIENCE.272","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.272","url":null,"abstract":"Our understanding of angiogenic signalling has been significantly enhanced through studies of a rare genetic disorder called Tuberous Sclerosis Complex (TSC). TSC patients are predisposed to highly vascularised tumours, where renal angiomyolipomas produce high levels of vascular endothelial growth factor (VEGF) that can be readily detected. It is well established that VEGF is driven through hypoxic signalling, with the transcription factor hypoxia inducible factor-1α (HIF-1α) playing a crucial role in its expression. Early studies using cell line models of TSC uncovered that the mammalian target of rapamycin complex 1 (mTORC1) is a key mediator of HIF-1α synthesis, and highlighted the anti-angiogenic properties of mTORC1 inhibitors [1]. Herein we review our recent findings characterising mTORC1 mediated regulation of HIF-1α and discuss the clinical implications of our work. \u0000 \u0000We demonstrated that mTORC1 drives HIF-1α expression via three mechanisms, promoting not only the transcription of HIF-1α mRNA via signal transducer and activator of transcription 3 (STAT3), but also its translation via both eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). This drive in HIF-1α activity downstream of mTORC1 explains why the tumours which present in TSC are so heavily vascularised, and accounts for the anti-tumorigenic properties of mTOR inhibitors used in this setting. In concordance with this, we observe a 10 fold-increase in HIF-1α transcriptional activity under hypoxia with TSC2 loss, highlighting the significant impact mTORC1 activation can have on HIF-1α. \u0000 \u0000Whilst mTORC1 can promote the transcriptional activity of STAT3 through direct phosphorylation of Ser727, STAT3 is also subject to regulation from a number of different cytokines and growth factors which signal through the receptor tyrosine kinase JAK2 [2]. Both JAK2/STAT3 and mTORC1 signalling pathways are frequently activated in a wide range of malignancies and converge at the level of HIF-1α (see Figure ​Figure1).1). Whilst mTOR inhibitors are effective at blocking Ser727 phosphorylation of STAT3, we were able to completely abolish HIF-1α expression by targeting both the JAK2-mediated Tyr705 phosphorylation site and the mTORC1-mediated Ser727 site. Our work indicates that targeting STAT3 in parallel to mTORC1 could enhance the anti-angiogenic and anti-tumorigenic properties of mTOR inhibitors that are currently in clinical use [3]. \u0000 \u0000 \u0000 \u0000Figure 1 \u0000 \u0000Multifaceted regulation of HIF-1α/VEGF-A via mTORC1 and STAT3 \u0000 \u0000 \u0000 \u0000Growth of tumours in renal cell carcinoma (RCC) is highly dependent on mTORC1, HIF and VEGF which drive a pro-angiogenic response. In the microenvironment of the kidney, angiogenic signalling is crucial for metabolic transformation and malignancy. Although there has been much investment into drug discovery and the development of inhibitors that directly inhibit HIF, none of these compounds are currently suitable for clinical use. C","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"44 1","pages":"913 - 914"},"PeriodicalIF":0.0,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90582742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of ICAM-2 in neuroblastoma","authors":"K. Yoon, A. Miller, K. Kreitzburg","doi":"10.18632/ONCOSCIENCE.273","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.273","url":null,"abstract":"The role of immunoglobulin superfamily cell adhesion molecules (CAMs) in facilitating immune responses in normal and tumor cells is well established. Cell adhesion molecule-1 (CADM1), for example, suppresses development of mouse mammary tumor cell metastasis by interacting with CD8+ T cells in immune-competent hosts [1]. Similarly, co-expression of Intercellular Adhesion Molecule-2 (ICAM-2) and chemokine C-X-C motif ligand 17 (CXCL17) elicits anti-tumor immune responses and suppresses tumor growth [2]. Although controversial, current literature suggests that proteins of the immunoglobulin superfamily CAMs also have functions that may well be distinct from their roles in mediating immune responses. Junctional adhesion molecule-A (JAM-A), for example, negatively regulates breast cancer cell invasiveness by disrupting tight junctions [3]; and a member of the B7 family of the immunoglobulin superfamily proteins, B7-H3, impairs osteogenic differentiation in vitro and in vivo [4]. \u0000 \u0000Our lab demonstrated that ICAM-2 inhibited the development of disseminated neuroblastoma tumors in a preclinical model of metastatic neuroblastoma [5-7]. This inhibition depended on the interaction of ICAM-2 with the actin cytoskeletal linker protein α-actinin, an interaction that inhibited cell motility [7]. Ectopic expression of ICAM-2 did not affect the tumorigenic potential of neuroblastoma cells [7]. Importantly, immunohistochemical analyses of primary neuroblastoma tumor specimens demonstrated that neuroblastoma cells expressing ICAM-2 are phenotypically and histologically those recognized clinically to have limited metastatic potential [5]. Since metastatic disease is responsible for >90% of cancer-related deaths for multiple types of solid tumors, we suggest that elucidation of the molecular mechanism by which ICAM-2 suppresses the metastatic potential of neuroblastoma cells would identify proteins or pathways that might be exploited therapeutically to prevent metastatic disease progression. \u0000 \u0000In normal tissues ICAM-2 is expressed predominantly by neovascular endothelial cells, and at lower levels by established vasculature and some leukocytes. The 202 amino acids comprising its extracellular domain mediate binding of ICAM-2 on endothelial cells to β2-integrins on the surface of leukocytes, to facilitate migration of neutrophils through the vascular endothelium as a component of immune reactions [8]. In neuroblastoma cells ICAM-2 inhibits cell motility independent of immune response, as we observed this inhibition in wound healing and modified Boyden chamber assays in vitro, assays that clearly lack an immune component [5,7]. \u0000 \u0000In silico modeling indicated that ICAM-2 with mutations in the proposed α-actinin binding domain had a more ‘closed’ configuration than the wild type protein, and predicted that these ICAM-2 mutants would not interact with α-actinin [7]. Co-immunoprecipitation experiments confirmed in silico predictions [7]. In support of these findings, t","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"17 1","pages":"915 - 916"},"PeriodicalIF":0.0,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87665668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting BCL6 and STAT3 in triple negative breast cancer: the one-two punch?","authors":"Sarah R Walker, D. Frank","doi":"10.18632/ONCOSCIENCE.270","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.270","url":null,"abstract":"Breast cancer remains the second leading cause of cancer deaths in women in the United States. Triple negative breast cancer, tumors lacking estrogen receptor, progesterone receptor, and Her2, only comprise about 20–30% of breast tumors diagnosed. However, due to the lack of specific targeted therapy as exists for ER+ or Her2+ tumors, they account for many of the breast cancer deaths. To develop targeted therapy for triple negative breast cancer, inhibiting two targets may be necessary. \u0000 \u0000One new target of interest is the transcriptional modulator BCL6 which has been recently identified as playing an important role in breast cancer [1–3]. BCL6 has been characterized as a transcriptional repressor that recruits various corepressor complexes to repress its target genes; however, genes have also been identified that are upregulated by BCL6 [1, 2], including Zeb1 which is involved in promoting EMT [3]. While the roles of BCL6 in preventing terminal differentiation of B cells in the germinal center and promoting diffuse large B cell lymphoma are well known, little is currently known about the roles of BCL6 in solid tissue. BCL6 is amplified in ∼50% of breast tumors and is expressed in most breast cancer cell lines, including triple negative breast cancer cell lines [1]. Furthermore, BCL6 expression is correlated with disease progression and poor overall survival [2], and targeting BCL6 results in reduced growth and loss of breast cancer cell viability [1]. Importantly, triple negative breast cancer cell lines were among the most sensitive to BCL6 inhibition. In the normal mammary gland, BCL6 has been shown to prevent terminal differentiation and milk production, in part due to competition with signal transducer and activator of transcription 5 (STAT5) for regulation of target genes [4]. \u0000 \u0000STATs are latent transcription factors that remain in the cytoplasm until activated by tyrosine phosphorylation often via Jak kinases. They then translocate to the nucleus as an active dimer and modulate transcription of target genes. There are seven members of the STAT family and four members, STAT1, STAT3, STAT5a, and STAT5b regulate the expression of BCL6. While STAT1 and STAT3 upregulate BCL6 expression, STAT5 (5a and 5b) downregulates BCL6 expression [5]. All four STATs have been shown to play roles in breast cancer; however, STAT3 activation has been linked to more aggressive types. While STAT3 activation can occur in any subtype of breast cancer [5], STAT3 activation is restricted largely to triple negative breast cancer cell lines, and STAT3 signaling has been shown to be important for the survival of triple negative breast tumors [6]. \u0000 \u0000Both BCL6 and STAT3 play critical roles in triple negative breast cancer, including promoting survival and EMT, through modulating largely distinct target genes. Thus, could targeting these two factors together be a useful strategy for specifically treating triple negative breast cancer? Inhibition of BCL6 by siRNA or the ","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"79 1","pages":"912 - 912"},"PeriodicalIF":0.0,"publicationDate":"2015-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82403705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A predictive signature for therapy assignment and risk assessment in prostate cancer","authors":"D. Bonci, R. De Maria","doi":"10.18632/ONCOSCIENCE.271","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.271","url":null,"abstract":"Prostate cancer remains the second leading cause of death in men. It is imperative to improve patient management in identifying bio-markers for personalized treatment. We demonstrated miR-15/miR-16 loss and miR-21 up-regulation and deregulation of their target genes, which represent a promising signature for ameliorating therapy assignment and risk assessment in prostate cancer.","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"8 1","pages":"920 - 923"},"PeriodicalIF":0.0,"publicationDate":"2015-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86955882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-155 regulates tumor myeloid-derived suppressive cells","authors":"Siqi Chen, Yi Zhang, Bin Zhang","doi":"10.18632/ONCOSCIENCE.269","DOIUrl":"https://doi.org/10.18632/ONCOSCIENCE.269","url":null,"abstract":"MicroRNA is small non-coding RNA and can lead to translational repression or target degradation by base-pairing with complementary sequences of mRNA molecules. MicroRNA-155 (miR-155), one of the most studied microRNA, is the first one to be reported as oncogenic [1]. miR-155 is over expressed in a long list of both hematological and solid tumors and is of paramount importance in cancer diagnosis and prognosis. However, how miR-155 particularly in host immune system regulates the tumor progression remains poorly understood. Our study underscores a contextual role of miR-155 in regulating tumor growth and tumor immunity via distinct immune subsets within tumors [2]. We conclude that the balance of different effects between those immune cell populations, which are regulated by miR-155, appears to determine whether miR-155 promotes or inhibits tumor growth [2]. \u0000 \u0000We demonstrated that host miR-155 deficiency promoted antitumor T cell immunity in multiple transplanted tumor models. Further analysis of immune cell compartments revealed that miR-155 was required for the accumulation and suppressive function of myeloid-derived suppressive cells (MDSC) in the tumor microenvironment. Apart from the direct modulation on MDSC, miR-155 was also required for the MDSC-mediated CD4+Foxp3+ regulatory T cells (Treg) induction. On the other hand, miR-155 deficiency hampered the antitumor responses of both dendritic cells and T cells. Therefore, it appears that in our tumor models, miR-155 mediated a dominant immunosuppressive effect by MDSC, leading to the enhanced overall antitumor immunity in miR-155 deficient hosts. \u0000 \u0000Reduced colon inflammation and decreased colorectal carcinogenesis were also found in miR-155 deficient mice when azoxymethane (AOM) and dextran sodium sulphate (DSS) were combined to induce colon lesions. Furthermore, miR-155 was upregulated in MDSC either from tumor-bearing hosts or generated from bone marrow progenitors by GM-CSF and IL-6. These results support the notion that miR-155 is a prototypical microRNA bridging inflammation and cancer development [3]. Although miR-155 may regulate tumor growth in an intrinsic manner, it is likely that inflammation promotes the accumulation of functional MDSC by increased miR-155 that dampens the immune surveillance and antitumor immunity, thereby facilitating tumor growth. \u0000 \u0000To identify the molecular mechanisms by which miR-155 regulates MDSC (Figure ​(Figure1),1), we found that miR155 retained the suppressive activity of MDSCs through inhibiting SOCS1. Moreover, inverse correlations between miR-155 expression and SHIP-1/SOCS1 expression were established in MDSC. As SHIP-1 was recently reported as a target of miR155 specifically in MDSC expansion [4], these results suggest both SHIP-1 and SOCS1 as target genes of miR-155 during functional MDSC generation. SOCS1 also restricted arginase I activity [5], which otherwise would limit the efficiency of MDSC proinflammatory responses. Indeed, we showed that ","PeriodicalId":94164,"journal":{"name":"Oncoscience","volume":"21 1","pages":"910 - 911"},"PeriodicalIF":0.0,"publicationDate":"2015-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89357128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}