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Oncogenesis

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https://www.readbyqxmd.com/read/29748568/carf-enrichment-promotes-epithelial-mesenchymal-transition-via-wnt-%C3%AE-catenin-signaling-its-clinical-relevance-and-potential-as-a-therapeutic-target
#1
Rajkumar S Kalra, Anupama Chaudhary, A-Rum Yoon, Priyanshu Bhargava, Amr Omar, Sukant Garg, Chae-Ok Yun, Sunil C Kaul, Renu Wadhwa
CARF (Collaborator of ARF)/CDKN2AIP was discovered as a novel ARF-binding protein. It has been established as an essential cell survival, p53-, and cell proliferation-regulatory protein. Although a moderate upregulation of CARF caused growth arrest and senescence, its excessively enriched levels were shown to facilitate aggressive proliferation and malignant transformation of cancer cells. Here, we examined the relevance of CARF levels in clinical tumors and found its amplification (both at gene and transcript levels) in a variety of invasive and metastatic malignancies...
May 11, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29735981/grainyhead-like-2-grhl2-knockout-abolishes-oral-cancer-development-through-reciprocal-regulation-of-the-map-kinase-and-tgf-%C3%AE-signaling-pathways
#2
Wei Chen, Kyung L Kang, Abdullah Alshaikh, Saaket Varma, Yi-Ling Lin, Ki-Hyuk Shin, Reuben Kim, Cun-Yu Wang, No-Hee Park, Katharina Walentin, Kai M Schmidt-Ott, Mo K Kang
Grainyhead-Like 2 (GRHL2) is an epithelial-specific transcription factor that regulates epithelial morphogenesis and differentiation. Prior studies suggested inverse regulation between GRHL2 and TGF-β in epithelial plasticity and potential carcinogenesis. Here, we report the role of GRHL2 in oral carcinogenesis in vivo using a novel Grhl2 knockout (KO) mouse model and the underlying mechanism involving its functional interaction with TGF-β signaling. We developed epithelial-specific Grhl2 conditional KO mice by crossing Grhl2 floxed mice with those expressing CreER driven by the K14 promoter...
May 8, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29712888/regulation-of-dna-damage-repair-and-lipid-uptake-by-cx-3-cr1-in-epithelial-ovarian-carcinoma
#3
Jia Xie, Hilal Gurler Main, Joelle D Sacks, Goda G Muralidhar, Maria V Barbolina
Failure of currently used cytotoxic chemotherapy is one of the main reasons behind high mortality from metastatic high grade serous ovarian carcinoma. We found that high expression of a receptor for fractalkine (CX3 CR1) significantly correlated with shorter survival of patients with serous ovarian carcinoma treated with cytotoxic DNA damage chemotherapies, and reduction of CX3 CR1 expression resulted in sensitization to several DNA damaging modalities, including x-ray radiation and cisplatin. Here, we show that CX3 CR1 plays a role in double-strand DNA break response and repair by regulating expression of RAD50 by a MYC-dependent mechanism...
May 1, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29691367/upregulation-of-sall4-by-egfr-activation-regulates-the-stemness-of-cd44-positive-lung-cancer
#4
Wenjing Du, Lan Ni, Baojun Liu, Ying Wei, Yubao Lv, Sujing Qiang, Jingcheng Dong, Xijun Liu
The transcriptional factor SALL4, an important stem cell regulator, is expressed in hematopoietic stem cells and various malignancies, but its role in EGFR-mutated NSCLCs has not been studied yet. Here, we report that the expression of Sal-like protein 4 (SALL4), was significantly higher in EGFR mutated lung tumors than in non-tumor tissue. SALL4-high lung cancer patients had poorer prognosis after surgery than SALL4-low patients. The expression of SALL4 could be induced by the activation of EGFR through the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway...
April 25, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29674704/mek-inhibitors-overcome-resistance-to-bet-inhibition-across-a-number-of-solid-and-hematologic-cancers
#5
Anastasia Wyce, Jeanne J Matteo, Shawn W Foley, Daniel J Felitsky, Satyajit R Rajapurkar, Xi-Ping Zhang, Melissa C Musso, Susan Korenchuk, Natalie O Karpinich, Kathryn M Keenan, Melissa Stern, Lijoy K Mathew, Charles F McHugh, Michael T McCabe, Peter J Tummino, Ryan G Kruger, Christopher Carpenter, Olena Barbash
BET inhibitors exhibit broad activity in cancer models, making predictive biomarkers challenging to define. Here we investigate the biomarkers of activity of the clinical BET inhibitor GSK525762 (I-BET; I-BET762) across cancer cell lines and demonstrate that KRAS mutations are novel resistance biomarkers. This finding led us to combine BET with RAS pathway inhibition using MEK inhibitors to overcome resistance, which resulted in synergistic effects on growth and survival in RAS pathway mutant models as well as a subset of cell lines lacking RAS pathway mutations...
April 20, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29674660/the-ribosome-slow-beating-heart-of-cancer-stem-cell
#6
REVIEW
Amandine Bastide, Alexandre David
The ribosome has long been considered as a consistent molecular factory, with a rather passive role in the translation process. Recent findings have shifted this obsolete view, revealing a remarkably complex and multifaceted machinery whose role is to orchestrate spatiotemporal control of gene expression. Ribosome specialization discovery has raised the interesting possibility of the existence of its malignant counterpart, an 'oncogenic' ribosome, which may promote tumor progression. Here we weigh the arguments supporting the existence of an 'oncogenic' ribosome and evaluate its role in cancer evolution...
April 20, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29593255/stress-induced-phosphoprotein-1-acts-as-a-scaffold-protein-for-glycogen-synthase-kinase-3-beta-mediated-phosphorylation-of-lysine-specific-demethylase-1
#7
Chia-Lung Tsai, An-Shine Chao, Shih-Ming Jung, Chiao-Yun Lin, Angel Chao, Tzu-Hao Wang
Stress-induced phosphoprotein 1 (STIP1)-a co-chaperone of heat shock proteins-promotes cell proliferation and may act as an oncogenic factor. Similarly, glycogen synthase kinase-3 beta (GSK3β)-mediated phosphorylation of lysine-specific demethylase 1 (LSD1)-an epigenetic regulator-can contribute to the development of an aggressive cell phenotype. Owing to their ability to tether different molecules into functional complexes, scaffold proteins have a key role in the regulation of different signaling pathways in tumorigenesis...
March 29, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29593251/targeting-mdmx-and-pkc%C3%AE-to-improve-current-uveal-melanoma-therapeutic-strategies
#8
R C Heijkants, M Nieveen, K C 't Hart, A F A S Teunisse, A G Jochemsen
Uveal melanoma (UM) is the most frequent ocular cancer in adults, accounting for ~5% of the total melanoma incidence. Although the primary tumor is well treatable, patients frequently develop metastases for which no curative therapy exists. Highly activated protein kinase C (PKC) is a common feature of UM and has shown potential as therapeutic intervention for UM patients. Unfortunately, PKC inhibition as single treatment appears to have only limited clinical benefit. Combining PKC inhibition with activation of p53, which is rarely mutated in UM, by MDM2 inhibitors has shown promising results in vitro and in vivo...
March 29, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29593211/snail1-action-in-tumor-cells-influences-macrophage-polarization-and-metastasis-in-breast-cancer-through-altered-gm-csf-secretion
#9
Audrey Brenot, Brett L Knolhoff, David G DeNardo, Gregory D Longmore
The EMT inducer SNAIL1 regulates breast cancer metastasis and its expression in human primary breast tumor predicts for poor outcomes. During tumor progression SNAIL1 has multiple effects in tumor cells that can impact metastasis. An inflammatory tumor microenvironment also impacts metastasis and recently SNAIL1 has been implicated as modulating the secretion of cytokines that can influence the tumor immune infiltrate. Using a spontaneous genetic model of breast cancer metastasis and syngeneic orthotopic transplant experiments we show that the action of SNAIL1 in primary breast tumor cells is required for breast tumor growth and metastasis...
March 29, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540752/double-agents-genes-with-both-oncogenic-and-tumor-suppressor-functions
#10
Libing Shen, Qili Shi, Wenyuan Wang
The role of genetic components in cancer development is an area of interest for cancer biologists in general. Intriguingly, some genes have both oncogenic and tumor-suppressor functions. In this study, we systematically identified these genes through database search and text mining. We find that most of them are transcription factors or kinases and exhibit dual biological functions, e.g., that they both positively and negatively regulate transcription in cells. Some cancer types such as leukemia are over-represented by them, whereas some common cancer types such as lung cancer are under-represented by them...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540733/molecular-link-between-glucose-and-glutamine-consumption-in-cancer-cells-mediated-by-ctbp-and-sirt4
#11
Li Wang, Jing-Jing Li, Li-Yu Guo, Peipei Li, Zhiqiang Zhao, Haisheng Zhou, Li-Jun Di
Glucose and Glutamine are two essential ingredients for cell growth. However, it remains open for investigation whether there is a general mechanism that coordinates the consumption of glucose and glutamine in cancer cells. Glutamine is mainly metabolized through the glutaminolysis pathway and our previous report indicated that CtBP increases GDH activity and promotes glutaminolysis through repressing the expression of SIRT4, a well-known mitochondrion-located factor that inhibits glutaminolysis pathway. CtBP is known to be a sensor of intracellular metabolic status; we thus hypothesized that a consensus CtBP-SIRT4-GDH axis may mediate the crosstalk between glycolysis and glutaminolysis...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540699/%C3%AE-catenin-sumoylation-increases-i%C3%AE%C2%BAb%C3%AE-stability-and-inhibits-breast-cancer-progression
#12
Huan Chen, Zhaowei Xu, Xiahui Li, Yangyang Yang, Bowen Li, Yanan Li, Kangkai Xia, Jian Wang, Shujing Li, Miao Wang, Huijian Wu
α-catenin has been demonstrated to suppress several different types of cancers. Here we demonstrate that α-catenin is modified by SUMO protein, which covalently binds α-catenin at the carboxy terminus at lysine 870. Substitution of lysine 870 with arginine completely abolishes α-catenin SUMOylation. This modification can be removed by SENP1. However, α-catenin SUMOylation does not affect its stability and subcellular localization. In addition, we observed that the SUMOylation-deficient α-catenin mutant has a reduced interaction with IκBα which prevents subsequent ubiquitination of IκBα, and therefore a reduced suppression of expression of the NF-κB target genes TNF-α, IL-8, VEGF, and uPA...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540677/sumoylation-modulates-foxk2-mediated-paclitaxel-sensitivity-in-breast-cancer-cells
#13
Gabriela Nestal de Moraes, Zongling Ji, Lavender Y-N Fan, Shang Yao, Stefania Zona, Andrew D Sharrocks, Eric W-F Lam
The forkhead transcription factor FOXK2 plays a critical role in suppressing tumorigenesis and mediating cytotoxic drug action in breast cancer. However, the mechanism by which the biological function of FOXK2 is regulated remains poorly understood. Here, we investigated the role of SUMOylation in modulating FOXK2-mediated drug sensitivity. We identified SUMOylation consensus motifs within the FOXK2 sequence and constructed two SUMOylation-defective double mutants by converting lysine 527 and 633 to arginines and glutamic acid 529 and 635 to alanines, respectively...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540675/expression-of-lncrna-mir222hg-co-transcribed-from-the-mir-221-222-gene-promoter-facilitates-the-development-of-castration-resistant-prostate-cancer
#14
Tong Sun, Shin-Yi Du, Joshua Armenia, Fangfang Qu, Jingyu Fan, Xiaodong Wang, Teng Fei, Kazumasa Komura, Shirley X Liu, Gwo-Shu Mary Lee, Philip W Kantoff
Mechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) to castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role in modulating androgen receptor function during CRPC development. With further investigation, we characterized a putative promoter region located 23.3 kb upstream of the miR-221/222 gene, and this promoter is differentially activated in CRPC LNCaP-Abl cells, leading to the up-regulation of miR-221/222...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540671/phosphorylation-dependent-stabilization-of-mzf1-upregulates-n-cadherin-expression-during-protein-kinase-ck2-mediated-epithelial-mesenchymal-transition
#15
Hyeonseok Ko, Seongrak Kim, Kyungmi Yang, Kunhong Kim
Epithelial-mesenchymal transition (EMT) is a critical process in invasion and metastasis of cancer cells. E-cadherin to N-cadherin switching is considered a molecular hallmark of EMT. Recently, we reported that increased CK2 activity fully induces E-cadherin to N-cadherin switching, but the molecular mechanisms of N-cadherin upregulation are unknown. In this study, we examined how N-cadherin is upregulated by CK2. N-cadherin promoter analysis and ChIP analysis identified and confirmed myeloid zinc finger 1 (MZF1) as an N-cadherin transcription factor...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29540668/cigarette-smoke-stimulates-the-stemness-of-renal-cancer-stem-cells-via-sonic-hedgehog-pathway
#16
Weiwei Qian, Xiaochuan Kong, Tao Zhang, Dengdian Wang, Jin Song, Yuan Li, Xiaoting Li, Hao Geng, Jie Min, Qi Kong, Jie Liu, Zhiqi Liu, Daming Wang, Zhiqiang Zhang, Dexin Yu, Caiyun Zhong
Cancer stem cells (CSCs) are essentially responsible for tumor initiation, growth, progression, metastasis and recurrence, and cigarette smoke (CS) is closely involved in the occurrence and development of kidney cancer. However, the effect of CS on renal CSCs has not been elucidated yet. In the present study, tumorsphere formation assay was used to enrich renal CSCs from 786-O and ACHN cells. We illustrated that CS effectively promoted renal CSCs stemness by enhancing tumorsphere formation, increasing the expression of renal CSCs markers (CD133, CD44, ALDHA1, Oct4, and Nanog) and elevating CD133+ cell population...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29487290/src-mediated-regulation-of-the-pi3k-pathway-in-advanced-papillary-and-anaplastic-thyroid-cancer
#17
Thomas C Beadnell, Kelsey W Nassar, Madison M Rose, Erin G Clark, Brian P Danysh, Marie-Claude Hofmann, Nikita Pozdeyev, Rebecca E Schweppe
Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway...
February 28, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29472531/efficacy-of-the-highly-selective-focal-adhesion-kinase-inhibitor-bi-853520-in-adenocarcinoma-xenograft-models-is-linked-to-a-mesenchymal-tumor-phenotype
#18
Ulrich A Hirt, Irene C Waizenegger, Norbert Schweifer, Christian Haslinger, Daniel Gerlach, Jürgen Braunger, Ulrike Weyer-Czernilofsky, Heinz Stadtmüller, Ioannis Sapountzis, Gerd Bader, Andreas Zoephel, Bojan Bister, Anke Baum, Jens Quant, Norbert Kraut, Pilar Garin-Chesa, Günther R Adolf
Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, has attracted interest as a target for pharmacological intervention in malignant diseases. Here, we describe BI 853520, a novel ATP-competitive inhibitor distinguished by high potency and selectivity. In vitro, the compound inhibits FAK autophosphorylation in PC-3 prostate carcinoma cells with an IC50 of 1 nmol/L and blocks anchorage-independent proliferation of PC-3 cells with an EC50 of 3 nmol/L, whereas cells grown in conventional surface culture are 1000-fold less sensitive...
February 23, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29472530/histone-deacetylase-inhibitor-itf2357-leads-to-apoptosis-and-enhances-doxorubicin-cytotoxicity-in-preclinical-models-of-human-sarcoma
#19
Marta Di Martile, Marianna Desideri, Maria Grazia Tupone, Simonetta Buglioni, Barbara Antoniani, Carlotta Mastroiorio, Rita Falcioni, Virginia Ferraresi, Nicola Baldini, Roberto Biagini, Michele Milella, Daniela Trisciuoglio, Donatella Del Bufalo
Sarcomas are rare tumors with generally poor prognosis, for which current therapies have shown limited efficacy. Histone deacetylase inhibitors (HDACi) are emerging anti-tumor agents; however, little is known about their effect in sarcomas. By using established and patient-derived sarcoma cells with different subtypes, we showed that the pan-HDACi, ITF2357, potently inhibited in vitro survival in a p53-independent manner. ITF2357-mediated cell death implied the activation of mitochondrial apoptosis, as attested by induction of pro-apoptotic BH3-only proteins and a caspases-dependent mechanism...
February 23, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29472529/a-novel-microrna-identified-in-hepatocellular-carcinomas-is-responsive-to-lef1-and-facilitates-proliferation-and-epithelial-mesenchymal-transition-via-targeting-of-nfix
#20
Yaqi Hu, Xu Guo, Jinxia Wang, Yankun Liu, Huijie Gao, Hongxia Fan, Xiangyang Nong, Xi Yang, Min Liu, Shengping Li, Hua Tang
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers. It has been demonstrated that various cellular microRNAs (miRNAs) play an important role in HCC development. Here, we analyzed the miRNA profile in HCC tissues by Solexa sequencing, and we identified a novel microRNA, miR-HCC1, which is upregulated in HCC tissues. Further experiments showed that miR-HCC1 promoted HCC cell proliferation in vivo and in vitro, and migration and invasion resulting from the epithelial-mesenchymal transition (EMT) process...
February 23, 2018: Oncogenesis
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