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https://www.readbyqxmd.com/read/29755130/restoring-puma-induction-overcomes-kras-mediated-resistance-to-anti-egfr-antibodies-in-colorectal-cancer
#1
Kyle Knickelbein, Jingshan Tong, Dongshi Chen, Yi-Jun Wang, Sandra Misale, Alberto Bardelli, Jian Yu, Lin Zhang
Intrinsic and acquired resistance to anti-EGFR antibody therapy, frequently mediated by a mutant or amplified KRAS oncogene, is a significant challenge in the treatment of colorectal cancer (CRC). However, the mechanism of KRAS-mediated therapeutic resistance is not well understood. In this study, we demonstrate that clinically used anti-EGFR antibodies, including cetuximab and panitumumab, induce killing of sensitive CRC cells through p73-dependent transcriptional activation of the pro-apoptotic Bcl-2 family protein PUMA...
May 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29733853/p73-alternative-splicing-exploring-a-biological-role-for-the-c-terminal-isoforms
#2
REVIEW
Polina Vikhreva, Gerry Melino, Ivano Amelio
p73 (encoded by TP73 gene) is a p53 related protein that functions as a transcriptional factor. Similarly to p53, following DNA damage, p73 is stabilised, activated and controls expression of target genes that are involved in the regulation of cycle arrest and apoptosis. However great complexity to the function of this gene is given by the wide range of its non-tumour related roles, which include neurological development, ciliogenesis and fertility. From the structural point of view, p73 displays an intricate range of regulations because it can be expressed both as a N-terminally deleted dominant-negative isoforms and as multiple alternatively spliced C-terminal isoforms, that can include or not a sterile alfa motif (SAM) domain...
May 4, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29727714/inhibitory-effect-of-microrna-154-targeting-whsc1-on-cell-proliferation-of-human-skin-squamous-cell-carcinoma-through-mediating-the-p53-signaling-pathway
#3
Hong-Quan Chen, Dong Gao
OBJECTIVE: Skin squamous cell carcinoma (SCC) is a common, morbid, and frequently lethal malignancy and ranks as the sixth most deadly cancer worldwide. Hence, this study aims to explore the effect of microRNA-154 (miR-154) targeting WHSC1 on proliferation and apoptosis of SCC cells via the P53 signaling pathway. METHODS: The targeting relationship between WHSC1 and miR-154 was validated using dual-luciferase reporter assay. Normal human epidermal keratinocytes (NHEK) were included, and SCC A431 and SCC-15 cell lines were cultured and transfected with miR-154 mimic, miR-154 inhibitor or siRNA-WHSC1...
May 1, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29717080/correction-prima-1met-apr-246-displays-high-antitumor-activity-in-multiple-myeloma-by-induction-of-p73-and-noxa
#4
(no author information available yet)
No abstract text is available yet for this article.
May 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29668749/p73-like-its-p53-homolog-shows-preference-for-inverted-repeats-forming-cruciforms
#5
Jana Čechová, Jan Coufal, Eva B Jagelská, Miroslav Fojta, Václav Brázda
p73 is a member of the p53 protein family and has essential functions in several signaling pathways involved in development, differentiation, DNA damage responses and cancer. As a transcription factor, p73 achieves these functions by binding to consensus DNA sequences and p73 shares at least partial target DNA binding sequence specificity with p53. Transcriptional activation by p73 has been demonstrated for more than fifty p53 targets in yeast and/or human cancer cell lines. It has also been shown previously that p53 binding to DNA is strongly dependent on DNA topology and the presence of inverted repeats that can form DNA cruciforms, but whether p73 transcriptional activity has similar dependence has not been investigated...
2018: PloS One
https://www.readbyqxmd.com/read/29662640/potential-therapeutic-targets-of-tp53-gene-in-the-context-of-its-classically-canonical-functions-and-its-latest-non-canonical-functions-in-human-cancer
#6
REVIEW
Toshimichi Tanaka, Masahiko Watanabe, Keishi Yamashita
In normal tissue, p53 protein has a wide range of functions involving cell homeostasis; its mutation, however, permits a carcinogenic acquisition of function. TP53 gene mutation is a major genomic aberration in various human cancers and is a critical event in the multi-step carcinogenesis process. TP53 mutation is clinically relevant for the molecular classification of carcinogenesis, as most recently described rigorously by the Cancer Genome Atlas Research Network. TP53 gene mutation has been considered to work as a tumor suppressor gene through the loss of its transcriptional activity, which is designated as a canonical function...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29628507/%C3%AE-np73-enhances-hif-1%C3%AE-protein-stability-through-repression-of-the-ecv-complex
#7
Marina Stantic, Johanna Wolfsberger, Habib A M Sakil, Margareta T Wilhelm
Cellular responses to low oxygen conditions are mainly regulated by the Hypoxia-inducible factors (HIFs). Induction of HIF-1α in tumor cells activates the angiogenic switch and allows for metabolic adaptations. HIF-1α protein levels are tightly regulated through ubiquitin-mediated proteosomal degradation; however, high levels of HIF-1α is a common feature in many solid tumors and is thought to enhance cancer cell proliferation, migration, and survival. Here, we report that the oncogenic p73 isoform, ∆Np73, increases HIF-1α protein stability...
April 9, 2018: Oncogene
https://www.readbyqxmd.com/read/29620203/inhibition-of-dna%C3%A2-pk-activity-sensitizes-a549-cells-to-x%C3%A2-ray-irradiation-by-inducing-the-atm%C3%A2-dependent-dna-damage-response
#8
Lina Yang, Xinrui Yang, Yiwei Tang, Defu Zhang, Lijie Zhu, Shengnan Wang, Bo Wang, Tao Ma
Non‑small cell lung cancer (NSCLC) is radioresistant to X‑rays due to powerful cellular DNA damage repair mechanisms. DNA‑dependent protein kinase (DNA‑PK) is a key enzyme involved in DNA damage repair and the phenomenon and molecular mechanism of NSCLC radionsensitivity were investigated following inhibition of DNA‑PK activity. In the present study A549 cells were treated with the DNA‑PK inhibitor NU7026 and/or siRNA directed against ataxia telangiectasia mutated (ATM), followed by exposure to 4 Gy X‑ray irradiation...
March 29, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29615516/mutant-and-wild-type-p53-form-complexes-with-p73-upon-phosphorylation-by-the-kinase-jnk
#9
Eric R Wolf, Ciarán P McAtarsney, Kristin E Bredhold, Amber M Kline, Lindsey D Mayo
The transcription factors p53 and p73 are critical to the induction of apoptotic cell death, particularly in response to cell stress that activates c-Jun N-terminal kinase (JNK). Mutations in the DNA-binding domain of p53, which are commonly seen in cancers, result in conformational changes that enable p53 to interact with and inhibit p73, thereby suppressing apoptosis. In contrast, wild-type p53 reportedly does not interact with p73. We found that JNK-mediated phosphorylation of Thr81 in the proline-rich domain (PRD) of p53 enabled wild-type p53, as well as mutant p53, to form a complex with p73...
April 3, 2018: Science Signaling
https://www.readbyqxmd.com/read/29562599/epstein-barr-virus-gene-barf1-expression-is-regulated-by-the-epithelial-differentiation-factor-%C3%AE-np63%C3%AE-in-undifferentiated-nasopharyngeal-carcinoma
#10
Eveline Hoebe, Coral Wille, Stacy Hagemeier, Shannon Kenney, Astrid Greijer, Jaap Middeldorp
Epstein-Barr Virus (EBV) BamHI-A rightward frame 1 (BARF1) protein is considered a viral oncogene in epithelial cells and has immune-modulating properties. During viral lytic replication BARF1 is expressed as an early gene, regulated by the immediate early EBV protein R. However, in viral latency BARF1 is exclusively expressed in epithelial tumors such as nasopharyngeal (NPC) and gastric carcinoma (GC) but not in lymphomas, indicating that activation of the BARF1 promoter is cell type specific. Undifferentiated NPC is characterized by high expression of ΔNp63 isoforms of the epithelial differentiation marker p63, a member of the p53 family of transcription factors...
March 17, 2018: Cancers
https://www.readbyqxmd.com/read/29534752/teriflunomide-promotes-oligodendroglial-differentiation-and-myelination
#11
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29521232/role-of-mir-193a-in-cancer-complexity-and-factors-control-the-pattern-of-its-expression
#12
Afraa Mamoori, Vinod Gopalan, Alfred K-Y Lam
BACKGROUND: There is emerging data suggest that the non-coding RNA (microRNA 193a or miR-193a) plays key roles in different types of cancers. OBJECTIVE: This review aims to investigate the functional significance of miR-193a in different cancers according to the information of literature. METHOD: All the literature concerning miR-193a in cancer in PubMed are analysed. RESULTS: Several studies proved the association of miR-193a expression patterns with cancer's stages, grades, response to the chemotherapy and even patient survival...
March 7, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29518025/emerging-roles-of-p53-family-members-in-glucose-metabolism
#13
REVIEW
Yoko Itahana, Koji Itahana
Glucose is the key source for most organisms to provide energy, as well as the key source for metabolites to generate building blocks in cells. The deregulation of glucose homeostasis occurs in various diseases, including the enhanced aerobic glycolysis that is observed in cancers, and insulin resistance in diabetes. Although p53 is thought to suppress tumorigenesis primarily by inducing cell cycle arrest, apoptosis, and senescence in response to stress, the non-canonical functions of p53 in cellular energy homeostasis and metabolism are also emerging as critical factors for tumor suppression...
March 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29511339/p73-coordinates-with-%C3%AE-133p53-to-promote-dna-double-strand-break-repair
#14
Hongjian Gong, Yuxi Zhang, Kunpeng Jiang, Shengfan Ye, Shuming Chen, Qinghe Zhang, Jinrong Peng, Jun Chen
Tumour repressor p53 isoform Δ133p53 is a target gene of p53 and an antagonist of p53-mediated apoptotic activity. We recently demonstrated that Δ133p53 promotes DNA double-strand break (DSB) repair by upregulating transcription of the repair genes RAD51, LIG4 and RAD52 in a p53-independent manner. However, Δ133p53 lacks the transactivation domain of full-length p53, and the mechanism by which it exerts transcriptional activity independently of full-length p53 remains unclear. In this report, we describe the accumulation of high levels of both Δ133p53 and p73 (a p53 family member) at 24 h post γ-irradiation (hpi)...
March 6, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29508625/reactive-nitrogen-species-control-apoptosis-and-autophagy-in-k562-cells-implication-of-tap73%C3%AE-induction-in-controlling-autophagy
#15
Sampurna Datta, Subhamoy Chakraborty, Chiranjit Panja, Sanjay Ghosh
The biological outcome of nitric oxide (NO) and reactive nitrogen species (RNS) in regulating pro survival and pro death autophagic pathways still demand further investigation. In the present study, we investigated the effect of nitrosative stress in K562 cells using NO donor compound DETA-NONOate, peroxynitrite, and SIN-1. Exposure to NO, peroxynitrite, and SIN-1 caused decrease in K562 cell survival. NO induced autophagy but not apoptosis or necrosis in K562 cells. In contrast, peroxynitrite and SIN-1 treatment induced apoptosis in K562 cells...
March 23, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29497314/mir-1180-5p-regulates-apoptosis-of-wilms-tumor-by-targeting-p73
#16
Xiuyun Jiang, Huaicheng Li
Introduction: Wilms' tumor (WT), the most common childhood tumor, occurs in sporadic or familial forms. Recent findings reported that abnormal expression in microRNA (miRNA) suggests an important role of miRNAs during WT progress. MiRNAs are endogenous short-chain noncoding RNAs, which have been reported as key biomarkers for detecting tumor onset and progression. However, the functional role of miR-1180 in WT has remained unknown. Materials and methods: MTT and clonogenic survival assays were used to detect WT cell proliferation...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29458146/enhanced-anticancer-effects-of-scutellaria-barbata-d-don-in-combination-with-traditional-chinese-medicine-components-on-non-small-cell-lung-cancer-cells
#17
Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells...
May 10, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29452959/differential-expressions-of-mdm2-and-tap73-in-cancer-and-cancer-adjacent-tissues-in-patients-with-non-small-cell-lung-carcinoma
#18
B Wang, X Liu, H Liu, J Guo, T Zhang, N Zhou, Y Ma, H Yu, L Chen, Z Ren, K Fan, X Tian
AIM: To investigate the differences in mRNA and protein expressions of MDM2 (mouse double minute 2 homolog) and P73 in cancer and cancer-adjacent tissues in patients with non-small-cell lung carcinoma (NSCLC). MATERIALS AND METHODS: We compared the protein expressions of MDM2 and P73 in lung cancer and cancer-adjacent tissues in NSCLC patients by IHC (immunohistochemistry) and WB (Western blot). We divided the NSCLC patients into two subgroups, adenocarcinoma and squamous carcinoma...
February 13, 2018: Pulmonology
https://www.readbyqxmd.com/read/29434772/transcription-activated-p73-modulated-cyclin-d1-expression-leads-to-doxorubicin-resistance-in-gastric-cancer
#19
Zhi-Peng Ji, Ling Qiang, Jian-Liang Zhang
Gastric cancer (GC) is one of the leading types of cancer in terms of mortality cases worldwide. Doxorubicin (Dox), a common chemotherapy drug, is frequently used to treat GC; however, acquired resistance to Dox hinders the chemotherapeutic outcome and causes shorter survival in GC patients. Several Dox-resistant GC cell lines, including SGC7901, SNU-1 and SNU-5 were generated to investigate the mechanism of Dox resistance in GC. Various methods were used to test the response of Dox-resistant GC cells and parental cells, including flow cytometry, Cell Counting kit-8 assay, reverse transcription polymerase chain reaction and western blot analysis...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29412778/the-long-noncoding-rna-tp73-as1-interacted-with-mir-124-to-modulate-glioma-growth-by-targeting-inhibitor-of-apoptosis-stimulating-protein-of-p53
#20
Shuai Xiao, Rensheng Wang, Xiangwei Wu, Wen Liu, Shanshan Ma
P73 antisense RNA 1T (non-protein coding), known as TP73-AS1 or PDAM, is a long noncoding RNA (lncRNA), which may regulate apoptosis by regulation of p53-dependent antiapoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In this study, the effect of TP73-AS1 in human brain glioma cell lines and clinical tumor samples was detected so as to reveal its role and function. In this study, TP73-AS1 was specifically upregulated in brain glioma cell lines and promoted glioma cell growth through targeting miR-124...
February 2018: DNA and Cell Biology
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