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Oncogene

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https://www.readbyqxmd.com/read/28320108/mir-103-regulates-triple-negative-breast-cancer-cells-migration-and-invasion-through-targeting-olfactomedin-4
#1
Bin Xiong, Xuefeng Lei, Lei Zhang, Jia Fu
Our previous study showed olfactomedin 4 (OLFM4) suppressed triple-negative breast cancer cells migration, invasion and metastasis-associated protein MMP 9 expression. OLFM4 was identified as a potential target of miR-103 according to microRNA target databases and published studies. The aim of this study is to validate the relationship between miR-103 and OLFM4, and explore the function and clinical significance of miR-103 in triple-negative breast cancer patients. In our results, miR-103 negatively regulated OLFM4 expression by directly targeting its 3'-UTR...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#2
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319413/aberrant-promoter-hypermethylation-of-p16-survivin-and-retinoblastoma-in-gastric-cancer
#3
L Guo, C Huang, Q J Ji
BACKGROUND: Gastric cancer is common and can be found throughout the world. Notoriously like other cancers, gastric cancer is a consequence of cellular regulation disorder. Epigenetics, including many oncogenes or tumour suppressor genes, can provide some clues for this kind of disorder. DNA methylation, especially promoter methylation, which causes the silence/decrease of tumour related genes, has become a focus in various tumour types. The aim of this study was to investigate promoter methylation of certain genes: p16, survivin, retinoblastoma (Rb), all of which have been regarded as genes related to gastric cancer...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28319094/targeting-c-fos-and-dusp1-abrogates-intrinsic-resistance-to-tyrosine-kinase-inhibitor-therapy-in-bcr-abl-induced-leukemia
#4
Meenu Kesarwani, Zachary Kincaid, Ahmed Gomaa, Erika Huber, Sara Rohrabaugh, Zain Siddiqui, Muhammad F Bouso, Tahir Latif, Ming Xu, Kakajan Komurov, James C Mulloy, Jose A Cancelas, H Leighton Grimes, Mohammad Azam
Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and relapse occurs owing to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD stem or progenitor cells in the absence of oncogenic kinase signaling, a phenomenon referred to as intrinsic resistance, depends on diverse growth factors. Here we report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1)...
March 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28319071/xrn2-promotes-emt-and-metastasis-through-regulating-maturation-of-mir-10a
#5
H Zhang, Y Lu, E Chen, X Li, B Lv, H G Vikis, P Liu
MicroRNAs (miRNAs) have been proposed as critical regulatory molecules in the epithelial-mesenchymal transition (EMT) program. However, the roles of mature miRNA biogenesis during EMT process needs to be defined. Here we determined that increased expression of XRN2 induced EMT and promoted metastasis in vitro and in vivo. Furthermore, we uncovered that XRN2 functions as pro-metastatic gene, which accelerates miR-10a maturation by binding pre-miR-10a in a DICER-independent manner. These findings suggest that XRN2 is a novel regulator of EMT that contributes to the metastatic processes in lung cancer through a novel miRNA regulatory mechanism...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#6
J Kim, H Jin, J C Zhao, Y A Yang, Y Li, X Yang, X Dong, J Yu
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319069/the-branched-chain-amino-acid-transaminase-1-sustains-growth-of-antiestrogen-resistant-and-er%C3%AE-negative-breast-cancer
#7
V Thewes, R Simon, M Hlevnjak, M Schlotter, P Schroeter, K Schmidt, Y Wu, T Anzeneder, W Wang, P Windisch, M Kirchgäßner, N Melling, N Kneisel, R Büttner, U Deuschle, H P Sinn, A Schneeweiss, S Heck, S Kaulfuss, H Hess-Stumpp, J G Okun, G Sauter, A E Lykkesfeldt, M Zapatka, B Radlwimmer, P Lichter, M Tönjes
Antiestrogen-resistant and triple-negative breast tumors pose a serious clinical challenge because of limited treatment options. We assessed global gene expression changes in antiestrogen-sensitive compared with antiestrogen-resistant (two tamoxifen resistant and two fulvestrant resistant) MCF-7 breast cancer cell lines. The branched-chain amino acid transaminase 1 (BCAT1), which catalyzes the first step in the breakdown of branched-chain amino acids, was among the most upregulated transcripts in antiestrogen-resistant cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319068/iron-addiction-a-novel-therapeutic-target-in-ovarian-cancer
#8
D Basuli, L Tesfay, Z Deng, B Paul, Y Yamamoto, G Ning, W Xian, F McKeon, M Lynch, C P Crum, P Hegde, M Brewer, X Wang, L D Miller, N Dyment, F M Torti, S V Torti
Ovarian cancer is a lethal malignancy that has not seen a major therapeutic advance in over 30 years. We demonstrate that ovarian cancer exhibits a targetable alteration in iron metabolism. Ferroportin (FPN), the iron efflux pump, is decreased, and transferrin receptor (TFR1), the iron importer, is increased in tumor tissue from patients with high grade but not low grade serous ovarian cancer. A similar profile of decreased FPN and increased TFR1 is observed in a genetic model of ovarian cancer tumor-initiating cells (TICs)...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319067/the-histone-demethylase-kdm3a-and-its-downstream-target-mcam-promote-ewing-sarcoma-cell-migration-and-metastasis
#9
M Sechler, J K Parrish, D K Birks, P Jedlicka
Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319066/nucleus-accumbens-associated-protein-1-promotes-glycolysis-and-survival-of-hypoxic-tumor-cells-via-the-hdac4-hif-1%C3%AE-axis
#10
Y Zhang, Y-J Ren, L-C Guo, C Ji, J Hu, H-H Zhang, Q-H Xu, W-D Zhu, Z-J Ming, Y-S Yuan, X Ren, J Song, J-M Yang
Nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the BTB/POZ gene family, has emerging roles in cancer. In this study, we identified the NAC1-HDAC4-HIF-1α axis as an important pathway in regulating glycolysis and hypoxic adaptation in tumor cells. We show that nuclear NAC1 binds to histone deacetylase type 4 (HDAC4), hindering phosphorylation of HDAC4 at Ser(246) and preventing its nuclear export that leads to cytoplasmic degradation of the deacetylase. Accumulation of HDAC4 in the nuclei results in an attenuation of HIF-1α acetylation, enhancing the stabilization and transcriptional activity of HIF-1α and strengthening adaptive response of cells to hypoxia...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319065/the-drebrin-eb3-pathway-drives-invasive-activity-in-prostate-cancer
#11
A E Dart, D C Worth, G Muir, A Chandra, J D Morris, C McKee, C Verrill, R J Bryant, P R Gordon-Weeks
Prostate cancer is the most common cancer in men and the metastatic form of the disease is incurable. We show here that the drebrin/EB3 pathway, which co-ordinates dynamic microtubule/actin filament interactions underlying cell shape changes in response to guidance cues, plays a role in prostate cancer cell invasion. Drebrin expression is restricted to basal epithelial cells in benign human prostate but is upregulated in luminal epithelial cells in foci of prostatic malignancy. Drebrin is also upregulated in human prostate cancer cell lines and co-localizes with actin filaments and dynamic microtubules in filopodia of pseudopods of invading cells under a chemotactic gradient of the chemokine CXCL12...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319064/oct4-controls-mitotic-stability-and-inactivates-the-rb-tumor-suppressor-pathway-to-enhance-ovarian-cancer-aggressiveness
#12
E Comisso, M Scarola, M Rosso, S Piazza, S Marzinotto, Y Ciani, M Orsaria, L Mariuzzi, C Schneider, S Schoeftner, R Benetti
OCT4 (Octamer-binding transcription factor 4) is essential for embryonic stem cell self-renewal. Here we show that OCT4 increases the aggressiveness of high-grade serous ovarian cancer (HG-SOC) by inactivating the Retinoblastoma tumor suppressor pathway and enhancing mitotic stability in cancer cells. OCT4 drives the expression of Nuclear Inhibitor of Protein Phosphatase type 1 (NIPP1) and Cyclin F (CCNF) that together inhibit Protein Phosphatase 1 (PP1). This results in pRB hyper-phosphorylation, accelerated cell proliferation and increased in vitro tumorigenicity of ovarian cancer cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319063/compromised-brca1-palb2-interaction-is-associated-with-breast-cancer-risk
#13
T K Foo, M Tischkowitz, S Simhadri, T Boshari, N Zayed, K A Burke, S H Berman, P Blecua, N Riaz, Y Huo, Y C Ding, S L Neuhausen, B Weigelt, J S Reis-Filho, W D Foulkes, B Xia
The major breast cancer suppressor proteins BRCA1 and BRCA2 play essential roles in homologous recombination (HR)-mediated DNA repair, which is thought to be critical for tumor suppression. The two BRCA proteins are linked by a third tumor suppressor, PALB2, in the HR pathway. While truncating mutations in these genes are generally pathogenic, interpretation of missense variants remains a challenge. To date, patient-derived missense variants that disrupt PALB2 binding have been identified in BRCA1 and BRCA2; however, there has not been sufficient evidence to prove their pathogenicity in humans, and no variants in PALB2 that disrupt either its BRCA1 or BRCA2 binding have been reported...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319062/ctcf-genetic-alterations-in-endometrial-carcinoma-are-pro-tumorigenic
#14
A D Marshall, C G Bailey, K Champ, M Vellozzi, P O'Young, C Metierre, Y Feng, A Thoeng, A M Richards, U Schmitz, M Biro, R Jayasinghe, L Ding, L Anderson, E R Mardis, J E J Rasko
CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319061/ccdc178-promotes-hepatocellular-carcinoma-metastasis-through-modulation-of-anoikis
#15
X Hu, Y Zhao, L Wei, B Zhu, D Song, J Wang, L Yu, J Wu
Hepatocellular carcinoma (HCC) is one of the most malignant tumors with high rate of recurrence and metastasis. Coiled-coil domain-containing protein 178 (CCDC178) has been reported to be mutated in HCC, whereas its role in physiological and pathologic process, including in human cancer, remains largely unknown. Here, we found that CCDC178 is upregulated in HCC tissues and its overexpression is correlated with pathological stage (P=0.003). CCDC178 deficiency reduced the anchorage-independent growth and anoikis resistance of HCC cells, and inhibited the HCC metastasis in vivo...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#16
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28319059/camk2%C3%AE-in-intestinal-epithelial-cells-modulates-colitis-associated-colorectal-carcinogenesis-via-enhancing-stat3-activation
#17
X Ma, Z Meng, L Jin, Z Xiao, X Wang, W M Tsark, L Ding, Y Gu, J Zhang, B Kim, M He, X Gan, J E Shively, H Yu, R Xu, W Huang
Inflammation is one of the major risk factors for cancer. Here, we show that calcium/calmodulin-dependent protein kinase II gamma (CAMK2γ) in intestinal epithelial cells (IECs) modulates inflammatory signals and promotes colitis-associated cancer (CAC) in mice. We have identified CAMK2γ as a downstream target of colitis-induced WNT5A signaling. Furthermore, we have shown that CAMK2γ protects against intestine tissue injury by increasing IEC survival and proliferation. Calcium/calmodulin-dependent protein kinase II gamma knockout mice displayed reduced CAC...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318223/high-throughput-dual-screening-method-for-ras-activities-and-inhibitors
#18
Kari Kopra, Arjan J van Adrichem, Outi M H Salo-Ahen, Juha Peltonen, Krister Wennerberg, Harri J Härmä
Ras GTPases act as "molecular switches", alternating between inactive GDP-bound and active GTP-bound conformation. Ras-oncogenes were discovered over three decades ago, but there are still no effective therapies for Ras-driven cancers. Drug discovery strategies have so far been unsuccessful, due to a lack of suitable screening methodologies and well-defined binding pockets on the Ras proteins. Here, we addressed the former by introducing a homogeneous quenching resonance energy transfer (QRET) technique based screening strategy for Ras interfacial and competitive inhibitors...
March 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#19
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28317270/3q26-29-amplification-in-head-and-neck-squamous-cell-carcinoma-a-review-of-established-and-prospective-oncogenes
#20
REVIEW
Matthew A Davidson, Emma J Shanks
Head and neck cancer (HNSCC) is significantly underrepresented in worldwide cancer research, despite the fact that survival rates for the disease have remained static for over 50 years. Distant metastasis is often present at the time of diagnosis, and is the primary cause of death in cancer patients. In the absence of routine effective targeted therapies, the standard of care treatment remains chemoradiation in combination with (often disfiguring) surgery. A defining characteristic of HNSCC is the amplification of a region of chromosome 3 (3q26-29), which is consistently associated with poorer patient outcome...
March 19, 2017: FEBS Journal
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