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Oncogene

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https://www.readbyqxmd.com/read/29789718/pdlim7-and-cdh18-regulate-the-turnover-of-mdm2-during-cdk4-6-inhibitor-therapy-induced-senescence
#1
Mary E Klein, Mark A Dickson, Cristina Antonescu, Li-Xuan Qin, Scott J Dooley, Afsar Barlas, Katia Manova, Gary K Schwartz, Aimee M Crago, Samuel Singer, Andrew Koff, William D Tap
CDK4/6 inhibitors are being used to treat a variety of human malignancies. In well-differentiated and dedifferentiated liposarcoma their clinical promise is associated with their ability to downregulate the MDM2 protein. The downregulation of MDM2 following treatment with CDK4/6 inhibitors also induces many cultured tumor cell lines derived from different types of malignancies to progress from quiescence into senescence. Here we used cultured human cell lines and defined a role for PDLIM7 and CDH18, regulating MDM2 protein in CDK4/6 inhibitor-treated cells...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789717/multicellular-detachment-generates-metastatic-spheroids-during-intra-abdominal-dissemination-in-epithelial-ovarian-cancer
#2
Sara Al Habyan, Christina Kalos, Joseph Szymborski, Luke McCaffrey
Ovarian cancer is the most lethal gynecological cancer, where survival rates have had modest improvement over the last 30 years. Metastasis of cancer cells is a major clinical problem, and patient mortality occurs when ovarian cancer cells spread beyond the confinement of ovaries. Disseminated ovarian cancer cells typically spread within the abdomen, where ascites accumulation aids in their transit. Metastatic ascites contain multicellular spheroids, which promote chemo-resistance and recurrence. However, little is known about the origin and mechanisms through which spheroids arise...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789716/xct-slc7a11-mediated-metabolic-reprogramming-promotes-non-small-cell-lung-cancer-progression
#3
Xiangming Ji, Jun Qian, S M Jamshedur Rahman, Peter J Siska, Yong Zou, Bradford K Harris, Megan D Hoeksema, Irina A Trenary, Chen Heidi, Rosana Eisenberg, Jeffrey C Rathmell, Jamey D Young, Pierre P Massion
Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789715/shared-and-independent-functions-of-apkc%C3%AE-and-par3-in-skin-tumorigenesis
#4
Susanne Vorhagen, Dominik Kleefisch, Oana-Diana Persa, Annika Graband, Alexandra Schwickert, Michael Saynisch, Michael Leitges, Carien M Niessen, Sandra Iden
The polarity proteins Par3 and aPKC are key regulators of processes altered in cancer. Par3/aPKC are thought to dynamically interact with Par6 but increasing evidence suggests that aPKC and Par3 also exert complex-independent functions. Whereas aPKCλ serves as tumor promotor, Par3 can either promote or suppress tumorigenesis. Here we asked whether and how Par3 and aPKCλ genetically interact to control two-stage skin carcinogenesis. Epidermal loss of Par3, aPKCλ, or both, strongly reduced tumor multiplicity and increased latency but inhibited invasion to similar extents, indicating that Par3 and aPKCλ function as a complex to promote tumorigenesis...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789714/estrogen-receptor-%C3%AE-promotes-renal-cell-carcinoma-progression-via-regulating-lncrna-hotair-mir-138-200c-204-217-associated-cerna-network
#5
Jie Ding, Chiuan-Ren Yeh, Yin Sun, Changyi Lin, Joshua Chou, Zhenyu Ou, Chawnshang Chang, Jun Qi, Shuyuan Yeh
Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789713/upregulation-of-the-long-noncoding-rna-foxd2-as1-promotes-carcinogenesis-by-epigenetically-silencing-ephb3-through-ezh2-and-lsd1-and-predicts-poor-prognosis-in-gastric-cancer
#6
Tong-Peng Xu, Wen-Yu Wang, Pei Ma, You Shuai, Kun Zhao, Yan-Fen Wang, Wei Li, Rui Xia, Wen-Ming Chen, Er-Bao Zhang, Yong-Qian Shu
Accumulating data indicate that long noncoding RNAs (lncRNAs) serve as important modulators in biological processes and are dysregulated in diverse tumors. The function of FOXD2-AS1 in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1 enrichment was upregulated markedly in GC and positively correlated with a large tumor size, a later pathologic stage, and a poor prognosis. Gene-set enrichment analysis (GSEA) in GEO datasets uncovered that cell cycle and DNA replication associated genes were enriched in patients with high FOXD2-AS1 expression...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789719/selective-vulnerability-of-the-primitive-meningeal-layer-to-prenatal-smo-activation-for-skull-base-meningothelial-meningioma-formation
#7
Julien Boetto, Caroline Apra, Franck Bielle, Matthieu Peyre, Michel Kalamarides
Somatic activating mutations of smoothened (SMO), a component of the embryonic sonic hedgehog (SHH) signaling pathway, are found in 3-5% of grade I meningiomas, most of them corresponding to meningothelial meningiomas located at the anterior skull base. By generating different developmental stage-specific conditional activations in mice, we define a restricted developmental window during which conditional activation of Smo in Prostaglandin D2-synthase-positive mesoderm-derived meningeal layer of the skull base results in meningothelial meningioma formation...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29786078/targeting-the-upstream-transcriptional-activator-of-pd-l1-as-an-alternative-strategy-in-melanoma-therapy
#8
Bo Zhu, Liming Tang, Shuyang Chen, Chengqian Yin, Shiguang Peng, Xin Li, Tongzheng Liu, Wei Liu, Changpeng Han, Lukasz Stawski, Zhi-Xiang Xu, Guangbiao Zhou, Xiang Chen, Xiumei Gao, Colin R Goding, Nan Xu, Rutao Cui, Peng Cao
Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2)...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29786077/tumor-derived-exosomes-promote-tumor-self-seeding-in-hepatocellular-carcinoma-by-transferring-mirna-25-5p-to-enhance-cell-motility
#9
Hao Liu, Wei Chen, Xiao Zhi, En-Jiang Chen, Tao Wei, Jian Zhang, Jian Shen, Li-Qiang Hu, Bin Zhao, Xin-Hua Feng, Xue-Li Bai, Ting-Bo Liang
Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell-cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells...
May 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29780169/mediator-kinase-cdk8-cdk19-drives-yap1-dependent-bmp4-induced-emt-in-cancer
#10
Anne Serrao, Laura M Jenkins, Alexander A Chumanevich, Ben Horst, Jiaxin Liang, Michael L Gatza, Nam Y Lee, Igor B Roninson, Eugenia V Broude, Karthikeyan Mythreye
CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition (EMT) is critically dependent on matrix rigidity and YAP1 in a wide spectrum of cancer models. We find that both genetic and pharmacological inhibition of CDK8 and its homologous twin kinase CDK19 leads to abrogation of BMP-induced EMT...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29780168/lox-catalyzed-collagen-stabilization-is-a-proximal-cause-for-intrinsic-resistance-to-chemotherapy
#11
Leonie Rossow, Simona Veitl, Sandra Vorlová, Jacqueline K Wax, Anja E Kuhn, Verena Maltzahn, Berin Upcin, Franziska Karl, Helene Hoffmann, Sabine Gätzner, Matthias Kallius, Rajender Nandigama, Daniela Scheld, Ster Irmak, Sabine Herterich, Alma Zernecke, Süleyman Ergün, Erik Henke
The potential of altering the tumor ECM to improve drug response remains fairly unexplored. To identify targets for modification of the ECM aiming to improve drug response and overcome resistance, we analyzed expression data sets from pre-treatment patient cohorts. Cross-evaluation identified a subset of chemoresistant tumors characterized by increased expression of collagens and collagen-stabilizing enzymes. We demonstrate that strong collagen expression and stabilization sets off a vicious circle of self-propagating hypoxia, malignant signaling, and aberrant angiogenesis that can be broken by an appropriate auxiliary intervention: Interfering with collagen stabilization by inhibition of lysyl oxidases significantly enhanced response to chemotherapy in various tumor models, even in metastatic disease...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29780167/e-cadherin-in-contact-inhibition-and-cancer
#12
REVIEW
Alisha M Mendonsa, Tae-Young Na, Barry M Gumbiner
E-cadherin is a key component of the adherens junctions that are integral in cell adhesion and maintaining epithelial phenotype of cells. Homophilic E-cadherin binding between cells is important in mediating contact inhibition of proliferation when cells reach confluence. Loss of E-cadherin expression results in loss of contact inhibition and is associated with increased cell motility and advanced stages of cancer. In this review we discuss the role of E-cadherin and its downstream signaling in regulation of contact inhibition and the development and progression of cancer...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29780166/nudt21-negatively-regulates-psmb2-and-cxxc5-by-alternative-polyadenylation-and-contributes-to-hepatocellular-carcinoma-suppression
#13
Sheng Tan, Hua Li, Weijie Zhang, Yunying Shao, Yuan Liu, Haiyang Guan, Jun Wu, Yani Kang, Junsong Zhao, Qing Yu, Yunzhao Gu, Keshuo Ding, Min Zhang, Wenchang Qian, Yong Zhu, Huayong Cai, Changyu Chen, Peter E Lobie, Xiaodong Zhao, Jielin Sun, Tao Zhu
Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism and involved in many diseases, including cancer. CFIm25, a subunit of the cleavage factor I encoded by NUDT21, is required for 3'RNA cleavage and polyadenylation. Although it has been recently reported to be involved in glioblastoma tumor suppression, its roles and the underlying functional mechanism remain unclear in other types of cancer. In this study, we characterized NUDT21 in hepatocellular carcinoma (HCC). Reduced expression of NUDT21 was observed in HCC tissue compared to adjacent non-tumorous compartment...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29773903/circadian-regulator-nr1d2-regulates-glioblastoma-cell-proliferation-and-motility
#14
Min Yu, Wenjing Li, Qianqian Wang, Yan Wang, Fei Lu
Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773902/nedd9-promotes-oncogenic-signaling-a-stem-mesenchymal-gene-signature-and-aggressive-ovarian-cancer-growth-in-mice
#15
Rashid Gabbasov, Fang Xiao, Caitlin G Howe, Laura E Bickel, Shane W O'Brien, Daniel Benrubi, Thuy-Vy Do, Yan Zhou, Emmanuelle Nicolas, Kathy Q Cai, Samuel Litwin, Sachiko Seo, Erica A Golemis, Denise C Connolly
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) supports oncogenic signaling in a number of solid and hematologic tumors. Little is known about the role of NEDD9 in ovarian carcinoma (OC), but available data suggest elevated mRNA and protein expression in advanced stage high-grade cancers. We used a transgenic MISIIR-TAg mouse OC model combined with genetic ablation of Nedd9 to investigate its action in the development and progression of OC. A Nedd9-/- genotype delayed tumor growth rate, reduced incidence of ascites, and reduced expression and activation of signaling proteins including SRC, STAT3, E-cadherin, and AURKA...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773901/ets-1-promoter-associated-noncoding-rna-regulates-the-nono-erg-ets-1-axis-to-drive-gastric-cancer-progression
#16
Dan Li, Yajun Chen, Hong Mei, Wanju Jiao, Huajie Song, Lin Ye, Erhu Fang, Xiaojing Wang, Feng Yang, Kai Huang, Liduan Zheng, Qiangsong Tong
Emerging studies have indicated the essential functions of long noncoding RNAs (lncRNAs) during cancer progression. However, whether lncRNAs contribute to the upregulation of v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1), an established oncogenic protein facilitating tumor invasion and metastasis, in gastric cancer remains elusive. Herein, we identified Ets-1 promoter-associated noncoding RNA (pancEts-1) as a novel lncRNA associated with the gastric cancer progression via mining of publicly available datasets and rapid amplification of cDNA ends...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29773900/c5a-induces-a549-cell-proliferation-of-non-small-cell-lung-cancer-via-gdf15-gene-activation-mediated-by-gcn5-dependent-klf5-acetylation
#17
Chenhui Zhao, Yongting Li, Wen Qiu, Fengxia He, Weiming Zhang, Dan Zhao, Zhiwei Zhang, Erbao Zhang, Pei Ma, Yiqian Liu, Ling Ma, Fengming Yang, Yingwei Wang, Yongqian Shu
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29769618/inhibitor-of-apoptosis-proteins-iaps-mediate-collagen-type-xi-alpha-1-driven-cisplatin-resistance-in-ovarian-cancer
#18
Miran Rada, Sameera Nallanthighal, Jennifer Cha, Kerry Ryan, Jessica Sage, Catherine Eldred, Maria Ullo, Sandra Orsulic, Dong-Joo Cheon
Although, cisplatin resistance is a major challenge in the treatment of ovarian cancer, the precise mechanisms underlying cisplatin resistance are not fully understood. Collagen type XI alpha 1 (COL11A1), a gene encoding a minor fibrillar collagen of the extracellular matrix, is identified as one of the most upregulated genes in cisplatin-resistant ovarian cancer and recurrent ovarian cancer. However, the exact functions of COL11A1 in cisplatin resistance are unknown. Here we demonstrate that COL11A1 binds to integrin α1β1 and discoidin domain receptor 2 (DDR2) and activates downstream signaling pathways to inhibit cisplatin-induced apoptosis in ovarian cancer cells...
May 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29769617/a-new-method-of-identifying-glioblastoma-subtypes-and-creation-of-corresponding-animal-models
#19
Xia Zhou, Gonghua Li, Sanqi An, Wen-Xing Li, Huihui Yang, Yicheng Guo, Zhi Dai, Shaoxing Dai, Junjuan Zheng, Jingfei Huang, Antonio Iavarone, Xudong Zhao
Glioblastoma (GBM) accounts for up to 50% of brain parenchymal tumors. It is the most malignant type of brain cancer with very poor survival and limited remedies. Cancer subtyping is important for cancer research and therapy. Here, we report a new subtyping method for GBM based on the genetic alterations of CDKN2A and TP53 genes. CDKN2A and TP53 are the most frequently mutated genes with mutation rates of 60 and 30%, respectively. We found that patients with deletion of CDKN2A possess worse survival than those with TP53 mutation...
May 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#20
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
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