Dendritic cell (DC) dysfunction in cancer is a well-established phenomenon that is considered one of the main mechanisms of immune evasion. Defects in dendritic cells are caused primarily by tumor-derived factors present in the tumor microenvironment. However, the mechanisms that drive this process remain elusive. In our recent investigations, we reported that tumor-derived versican induces DC dysfunction through TLR2 activation. Ligation of TLR2 by tumor-derived factors sensitizes DCs to IL-6 and IL-10 by increasing their respective cytokine cell surface receptors expression, thus lowering the threshold of STAT3 activation. This mechanism reprograms sensitized DCs into immunosuppressive IL-10 producing cells. Our work revealed key molecular mechanisms of DC dysfunction in cancer and identified TLR2 as a relevant therapeutic target to improve DC immunogenicity and cancer immunotherapy.
{"title":"The role of TLR2 activation in promoting tumor dendritic cell dysfunction","authors":"Michael Tang, Jun Diao, M. Cattral","doi":"10.14800/CCM.1214","DOIUrl":"https://doi.org/10.14800/CCM.1214","url":null,"abstract":"Dendritic cell (DC) dysfunction in cancer is a well-established phenomenon that is considered one of the main mechanisms of immune evasion. Defects in dendritic cells are caused primarily by tumor-derived factors present in the tumor microenvironment. However, the mechanisms that drive this process remain elusive. In our recent investigations, we reported that tumor-derived versican induces DC dysfunction through TLR2 activation. Ligation of TLR2 by tumor-derived factors sensitizes DCs to IL-6 and IL-10 by increasing their respective cytokine cell surface receptors expression, thus lowering the threshold of STAT3 activation. This mechanism reprograms sensitized DCs into immunosuppressive IL-10 producing cells. Our work revealed key molecular mechanisms of DC dysfunction in cancer and identified TLR2 as a relevant therapeutic target to improve DC immunogenicity and cancer immunotherapy.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88828835","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}
Aromatase (CYP19) is the key enzyme in the biosynthesis of estrogens. In humans, it is expressed in a tissue- and promoter-specific manner. In hormone-dependent breast cancer, CYP19 is overexpressed through the activation of several additional promoters (PII, I.3 and I.7) that are normally inactive in the healthy mammary gland. In the normal mammary gland, low basal CYP19 expression is regulated by the I.4 promoter, which is also active in adipose tissue. Here, we highlight our recent study of the effects of neonicotinoid pesticides on the promoter-specific expression of CYP19 in various human in vitro models. We also discuss the implications of endocrine disruption by environmental chemicals for the development of hormone-dependent diseases, such as breast cancer.
{"title":"Effects of neonicotinoids on promoter-specific expression and activity of aromatase: implications for the development of hormone-dependent breast cancer","authors":"Élyse Caron-Beaudoin, J. Sanderson","doi":"10.14800/CCM.1216","DOIUrl":"https://doi.org/10.14800/CCM.1216","url":null,"abstract":"Aromatase (CYP19) is the key enzyme in the biosynthesis of estrogens. In humans, it is expressed in a tissue- and promoter-specific manner. In hormone-dependent breast cancer, CYP19 is overexpressed through the activation of several additional promoters (PII, I.3 and I.7) that are normally inactive in the healthy mammary gland. In the normal mammary gland, low basal CYP19 expression is regulated by the I.4 promoter, which is also active in adipose tissue. Here, we highlight our recent study of the effects of neonicotinoid pesticides on the promoter-specific expression of CYP19 in various human in vitro models. We also discuss the implications of endocrine disruption by environmental chemicals for the development of hormone-dependent diseases, such as breast cancer.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85430989","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}
A. Farina, L. Cappabianca, P. Ruggeri, L. Gneo, A. Mackay
There is growing evidence that the miss-localisation of receptor tyrosine kinase oncogenes underpins downstream oncogenic signaling. Here, we highlight our recent work characterising the mechanism that underpins miss-localisation and subsequent oncogenic activity of the oncogenic alternative TrkAIII splice variant of the tropomyosin related kinase A (TrkA) receptor, in human neuroblastoma cells. In primary neuroblastomas, expression of fully spliced TrkA associates with low-stage disease and better prognosis, whereas TrkAIII expression associates with advanced-stage disease and worse prognosis. In neuroblastoma models TrkA and TrkAIII exhibit opposite tumour suppressing and oncogenic activity, respectively. In an attempt to further understand the basis of this diametrically opposite behaviour, intracellular trafficking and activation TrkA and TrkAIII receptors was compared in SH-SY5Y neuroblastoma cells. We found that TrkAIII oncogenic activity originates from miss-localisation and spontaneous activation within the alternative membrane substrate context of the endoplasmic reticulum-Golgi intermediate (ERGIC)-COP-I vesicle compartment. This results from altered trafficking caused by interphase restricted spontaneous receptor activation, which impedes TrkAIII transport from the ERGIC to the Golgi network, in associated with retrograde transport of activated TrkAIII from the ERGIC back to the endoplasmic reticulum (ER). Therefore, spontaneous TrkAIII activation within ERGIC/COPI membranes, facilitated by omission of the extracellular D4 spontaneous activation-prevention domain, sets-up self-perpetuating TrkAIII recycling between the ER and ERGIC. This mechanism ensures continuous accumulation of this compromised receptors above the spontaneous activation threshold of the ERGIC/COPI compartment, resulting in oncogenic signaling through IP3K from this altered substrate context. Furthermore, chronic ER stress caused by TrkAIII recycling back to the ER induces a protective ER-stress response, and also the recruitment of active TrkAIII to the centrosome, altering centrosome behaviour. These different tumour-promoting mechanisms all result from miss-localization and spontaneous activation of TrkAIII within the alternative substrate context of the ERGIC/COPI compartment and can be prevented by TrkA tyrosine kinase inhibitors.
{"title":"The enemy from within: Mislocalization of a compromised receptor as a mechanism for TrkAIII oncogenic activity","authors":"A. Farina, L. Cappabianca, P. Ruggeri, L. Gneo, A. Mackay","doi":"10.14800/CCM.1205","DOIUrl":"https://doi.org/10.14800/CCM.1205","url":null,"abstract":"There is growing evidence that the miss-localisation of receptor tyrosine kinase oncogenes underpins downstream oncogenic signaling. Here, we highlight our recent work characterising the mechanism that underpins miss-localisation and subsequent oncogenic activity of the oncogenic alternative TrkAIII splice variant of the tropomyosin related kinase A (TrkA) receptor, in human neuroblastoma cells. In primary neuroblastomas, expression of fully spliced TrkA associates with low-stage disease and better prognosis, whereas TrkAIII expression associates with advanced-stage disease and worse prognosis. In neuroblastoma models TrkA and TrkAIII exhibit opposite tumour suppressing and oncogenic activity, respectively. In an attempt to further understand the basis of this diametrically opposite behaviour, intracellular trafficking and activation TrkA and TrkAIII receptors was compared in SH-SY5Y neuroblastoma cells. We found that TrkAIII oncogenic activity originates from miss-localisation and spontaneous activation within the alternative membrane substrate context of the endoplasmic reticulum-Golgi intermediate (ERGIC)-COP-I vesicle compartment. This results from altered trafficking caused by interphase restricted spontaneous receptor activation, which impedes TrkAIII transport from the ERGIC to the Golgi network, in associated with retrograde transport of activated TrkAIII from the ERGIC back to the endoplasmic reticulum (ER). Therefore, spontaneous TrkAIII activation within ERGIC/COPI membranes, facilitated by omission of the extracellular D4 spontaneous activation-prevention domain, sets-up self-perpetuating TrkAIII recycling between the ER and ERGIC. This mechanism ensures continuous accumulation of this compromised receptors above the spontaneous activation threshold of the ERGIC/COPI compartment, resulting in oncogenic signaling through IP3K from this altered substrate context. Furthermore, chronic ER stress caused by TrkAIII recycling back to the ER induces a protective ER-stress response, and also the recruitment of active TrkAIII to the centrosome, altering centrosome behaviour. These different tumour-promoting mechanisms all result from miss-localization and spontaneous activation of TrkAIII within the alternative substrate context of the ERGIC/COPI compartment and can be prevented by TrkA tyrosine kinase inhibitors.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87160739","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}
The role of the secreted matricellular molecule osteopontin (OPN) and its receptor integrins in the pathogenesis of adult T-cell leukemia (ATL) and the possible applications of an anti-OPN monoclonal antibody (mAb) for ATL immunotherapy in NOD/Shi- scid , IL-2R g null (NOG) mice were investigated. Subcutaneous inoculation of ATL cell lines into NOG mice led to increased plasma levels of OPN, correlating well with metastasis of the inoculated cells and survival time. This result suggested that the xenograft NOG mouse model could be a useful system for in vivo assessment of the physiological role of OPN in ATL pathogenesis. Intraperitoneal administration of an anti-OPN mAb resulted in the inhibition of tumor growth, tumor invasion, and metastasis. In addition, the mAb treatment led to reduction in the number of fibroblasts expressing fibroblast activation protein. We have shown here a novel mAb-mediated therapeutic strategy targeting the interaction between OPN from stromal cells and integrins on the tumors of ATL patients. In this editorial research highlight, we also comment on the recent progress in the development of mAbs and their advanced counterparts, the antibody-drug conjugate, for the treatment of cancers.
研究了分泌的基质细胞分子骨桥蛋白(OPN)及其受体整合素在成人t细胞白血病(ATL)发病中的作用，以及抗OPN单克隆抗体(mAb)在NOD/Shi- scid, IL-2R g null (NOG)小鼠中用于ATL免疫治疗的可能应用。皮下接种ATL细胞系后，NOG小鼠血浆OPN水平升高，并与接种细胞的转移和存活时间密切相关。该结果提示，异种移植NOG小鼠模型可作为体内评估OPN在ATL发病机制中的生理作用的有效系统。腹腔注射抗opn单抗可抑制肿瘤生长、肿瘤侵袭和转移。此外，mAb处理导致表达成纤维细胞激活蛋白的成纤维细胞数量减少。我们在这里展示了一种新的单克隆抗体介导的治疗策略，靶向基质细胞的OPN和整合素对ATL患者肿瘤的相互作用。在这篇社论的研究重点中，我们还评论了单克隆抗体及其先进的对应物，抗体-药物偶联物，用于治疗癌症的最新进展。
{"title":"Antibody-mediated molecular-targeted therapy for adult T-cell leukemia: Recent progress and future challenges in the treatment of cancers","authors":"N. Maeda, A. Matsuda, K. Maenaka","doi":"10.14800/CCM.1201","DOIUrl":"https://doi.org/10.14800/CCM.1201","url":null,"abstract":"The role of the secreted matricellular molecule osteopontin (OPN) and its receptor integrins in the pathogenesis of adult T-cell leukemia (ATL) and the possible applications of an anti-OPN monoclonal antibody (mAb) for ATL immunotherapy in NOD/Shi- scid , IL-2R g null (NOG) mice were investigated. Subcutaneous inoculation of ATL cell lines into NOG mice led to increased plasma levels of OPN, correlating well with metastasis of the inoculated cells and survival time. This result suggested that the xenograft NOG mouse model could be a useful system for in vivo assessment of the physiological role of OPN in ATL pathogenesis. Intraperitoneal administration of an anti-OPN mAb resulted in the inhibition of tumor growth, tumor invasion, and metastasis. In addition, the mAb treatment led to reduction in the number of fibroblasts expressing fibroblast activation protein. We have shown here a novel mAb-mediated therapeutic strategy targeting the interaction between OPN from stromal cells and integrins on the tumors of ATL patients. In this editorial research highlight, we also comment on the recent progress in the development of mAbs and their advanced counterparts, the antibody-drug conjugate, for the treatment of cancers.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79349768","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}
Liver X Receptors (LXRs) and their ligands are known for their potential anticancer properties. Recently, our team underlined for the first time that these ligands induce colon cancer cell death through the activation of the inflammasome pathway and in an LXRβ-dependent manner. Moreover, a truncated form of the Retinoid X Receptor α (RXRα), t-RXRα, produced only in cancer cells and not in normal colon epithelial cells interacts with LXRβ to maintain it in the cytoplasm. This specific localization of LXRβ in colon cancer cells dictates their sensitivity towards LXR ligand cytotoxicity whereas its nuclear localization in normal colon epithelial cells prevent it. Our results highlight LXRβ subcellular localization as a promising marker for LXR ligand efficacy in colon cancer treatment.
{"title":"LXRβ subcellular localization: A new tool to investigate cancer cell response to LXR ligand-induced cytotoxicity?","authors":"V. Derangère, C. Rébé","doi":"10.14800/CCM.1200","DOIUrl":"https://doi.org/10.14800/CCM.1200","url":null,"abstract":"Liver X Receptors (LXRs) and their ligands are known for their potential anticancer properties. Recently, our team underlined for the first time that these ligands induce colon cancer cell death through the activation of the inflammasome pathway and in an LXRβ-dependent manner. Moreover, a truncated form of the Retinoid X Receptor α (RXRα), t-RXRα, produced only in cancer cells and not in normal colon epithelial cells interacts with LXRβ to maintain it in the cytoplasm. This specific localization of LXRβ in colon cancer cells dictates their sensitivity towards LXR ligand cytotoxicity whereas its nuclear localization in normal colon epithelial cells prevent it. Our results highlight LXRβ subcellular localization as a promising marker for LXR ligand efficacy in colon cancer treatment.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77229770","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}
The deubiquitinases (DUBs) are emerging targets for cancer therapy. An increasing number of DUB inhibitors were discovered to be potential anti-tumor agents. We recently identified that auranofin (Aur), a gold-containing compound used clinically to treat rheumatoid arthritis, is an inhibitor of proteasome-associated DUBs. Besides its inherent anti-arthritis effect, Aur has been shown to exhibit a predominant anti-tumor property in various cancer phenotypes. Hence, we were prompted to enhance the anti-cancer capability of this promising drug. Disulfiram (DSF) is currently being used clinically for the treatment of alcoholism. Recent studies suggested that DSF could potentiate the effect of some other chemotherapeutic agents. In a recent study, we unraveled that Aur and DSF in combination potently induced apoptosis of hepatoma cells both in vitro and in vivo, and the synergistic cytotoxicity is associated with endoplasmic reticulum (ER) stress, loss of MMP, and caspase activation. Hence, we have identified a synergism model between two clinical drugs DUB inhibitor Aur and DSF in the induction of apoptosis as a potentially novel anticancer strategy for clinical use in the future.
{"title":"Novel use of clinical drugs: Deubiquitinase inhibitor auranofin and disulfiram show synergistic anti-tumor effects in vitro and in vivo","authors":"Hongbiao Huang, Yuning Liao, Ningning Liu, Jianyu Cai, Xuejun Wang, Jinbao Liu","doi":"10.14800/CCM.1199","DOIUrl":"https://doi.org/10.14800/CCM.1199","url":null,"abstract":"The deubiquitinases (DUBs) are emerging targets for cancer therapy. An increasing number of DUB inhibitors were discovered to be potential anti-tumor agents. We recently identified that auranofin (Aur), a gold-containing compound used clinically to treat rheumatoid arthritis, is an inhibitor of proteasome-associated DUBs. Besides its inherent anti-arthritis effect, Aur has been shown to exhibit a predominant anti-tumor property in various cancer phenotypes. Hence, we were prompted to enhance the anti-cancer capability of this promising drug. Disulfiram (DSF) is currently being used clinically for the treatment of alcoholism. Recent studies suggested that DSF could potentiate the effect of some other chemotherapeutic agents. In a recent study, we unraveled that Aur and DSF in combination potently induced apoptosis of hepatoma cells both in vitro and in vivo, and the synergistic cytotoxicity is associated with endoplasmic reticulum (ER) stress, loss of MMP, and caspase activation. Hence, we have identified a synergism model between two clinical drugs DUB inhibitor Aur and DSF in the induction of apoptosis as a potentially novel anticancer strategy for clinical use in the future.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"129 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86767516","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}
We recently reported a study that identified the relevance of the large extracellular loop of tetraspanin 8 (TSPAN8-LEL) in metastatic colorectal cancer (mCRC) cell invasion. This study suggested a functional role for TSPAN8-LEL in mCRC cell invasion and the potential use of an antibody to inhibit the invasion of TSPAN8-expressing mCRCs. In this research highlight, we describe TSPAN8-LEL as a novel potential therapeutic target in mCRCs. TSPAN8 plays a key role in TSPAN8-expressing HCT116 mCRC cell invasion. Among its two extracellular loops, TSPAN8-LEL is the key domain that regulates HCT116 mCRC cell invasion. In addition, a fully human monoclonal antibody specific to TSPAN8-LEL (anti-TSPAN8-LEL HuMab) efficiently suppresses the invasion of HCT116 and LoVo mCRC cell lines more potently than HCT-8 and SW480 non-mCRC cell lines. These results indicate that targeting TSPAN8-LEL may suppress the invasion of TSPAN8-expressing mCRCs. Therefore, TSPAN8 may be a novel potential therapeutic target for antibody-based mCRC therapy.
{"title":"A large extracellular loop of TSPAN8 as a novel therapeutic target for metastatic colorectal cancer cell invasion","authors":"Taek-Keun Kim, Sukmook Lee","doi":"10.14800/CCM.1196","DOIUrl":"https://doi.org/10.14800/CCM.1196","url":null,"abstract":"We recently reported a study that identified the relevance of the large extracellular loop of tetraspanin 8 (TSPAN8-LEL) in metastatic colorectal cancer (mCRC) cell invasion. This study suggested a functional role for TSPAN8-LEL in mCRC cell invasion and the potential use of an antibody to inhibit the invasion of TSPAN8-expressing mCRCs. In this research highlight, we describe TSPAN8-LEL as a novel potential therapeutic target in mCRCs. TSPAN8 plays a key role in TSPAN8-expressing HCT116 mCRC cell invasion. Among its two extracellular loops, TSPAN8-LEL is the key domain that regulates HCT116 mCRC cell invasion. In addition, a fully human monoclonal antibody specific to TSPAN8-LEL (anti-TSPAN8-LEL HuMab) efficiently suppresses the invasion of HCT116 and LoVo mCRC cell lines more potently than HCT-8 and SW480 non-mCRC cell lines. These results indicate that targeting TSPAN8-LEL may suppress the invasion of TSPAN8-expressing mCRCs. Therefore, TSPAN8 may be a novel potential therapeutic target for antibody-based mCRC therapy.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78376090","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}
Gap junctional intercellular communication built by hemichannels on cell membrane is a functional syncytium which allows rapid transfer of ions and molecules between cells. Recent findings have shown that gap junction proteins, and specifically Cx43, can play a significant role in cell migration, tissue formation and organ development, impacting adhesion and cytoskeletal rearrangements. Some literatures have shown that Cx43 was able to contribute to the treatment of gliomas by modulation of gap junctional communication. However, the exact cellular mechanism behind those pharmaceutical efficacies on Cx43 still remains unknown. Hereby, targeting Cx43 on astrocytes in gliomas is mainly discussed.
{"title":"Connexin43 in gap junctional intercellular communication in astrocytes and glioma cells","authors":"X. Ye, Zhen-Yu Zhang, Rui-Jin Yang, Qiu-Hua Jiang","doi":"10.14800/CCM.1241","DOIUrl":"https://doi.org/10.14800/CCM.1241","url":null,"abstract":"Gap junctional intercellular communication built by hemichannels on cell membrane is a functional syncytium which allows rapid transfer of ions and molecules between cells. Recent findings have shown that gap junction proteins, and specifically Cx43, can play a significant role in cell migration, tissue formation and organ development, impacting adhesion and cytoskeletal rearrangements. Some literatures have shown that Cx43 was able to contribute to the treatment of gliomas by modulation of gap junctional communication. However, the exact cellular mechanism behind those pharmaceutical efficacies on Cx43 still remains unknown. Hereby, targeting Cx43 on astrocytes in gliomas is mainly discussed.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88828265","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}
Posttranscriptional regulation of the biosynthesis of connexins, the building blocks of gap junctional channels, may occur by modulation of connexin mRNA stability and translation. To date, few RNA binding proteins and micro-RNAs (miRNAs) affecting connexin expression are known. In recent years, it has become clear that epigenetic processes are also essentially involved in connexin gene expression. In this review, we summarize recent knowledge on regulation of connexin expression by transcription factors and epigenetic mechanisms including microRNA.
{"title":"MicroRNAs as regulators of connexin-43 expression","authors":"X. Ye, Rui-Jin Yang, Zhen-Yu Zhang, Qiu-Hua Jiang","doi":"10.14800/CCM.1238","DOIUrl":"https://doi.org/10.14800/CCM.1238","url":null,"abstract":"Posttranscriptional regulation of the biosynthesis of connexins, the building blocks of gap junctional channels, may occur by modulation of connexin mRNA stability and translation. To date, few RNA binding proteins and micro-RNAs (miRNAs) affecting connexin expression are known. In recent years, it has become clear that epigenetic processes are also essentially involved in connexin gene expression. In this review, we summarize recent knowledge on regulation of connexin expression by transcription factors and epigenetic mechanisms including microRNA.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85558175","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}
Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the microRNAs that have been shown to positively and negatively regulate GBM invasion.
{"title":"Mechanisms of miRNA expression in regulating glioma invasion","authors":"X. Ye, Zhen-Yu Zhang, Rui-Jin Yang, Qiu-Hua Jiang","doi":"10.14800/CCM.1237","DOIUrl":"https://doi.org/10.14800/CCM.1237","url":null,"abstract":"Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the microRNAs that have been shown to positively and negatively regulate GBM invasion.","PeriodicalId":9576,"journal":{"name":"Cancer cell & microenvironment","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74532398","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}
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