Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Siân Jones,Xiaosong Zhang,D. Williams Parsons,D. Williams Parsons,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,Hirohiko Kamiyama,Antonio Jimeno,Seung-Mo Hong,Baojin Fu,Ming Tseh Lin,Eric S. Calhoun,Mihoko Kamiyama,Kimberly Walter,Tatiana Nikolskaya,Yuri Nikolsky,James Hartigan,Douglas Smith,Manuel Hidalgo,Steven D. Leach,Alison P. Klein,Elizabeth M. Jaffee,Michael Goggins,Anirban Maitra,Anirban Maitra,Christine A. Iacobuzio-Donahue,James R. Eshleman,Scott E. Kern,Ralph H. Hruban,Rachel Karchin,Nickolas Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +37 more
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TLDR
It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.Abstract:
There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 10(6) single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.read more
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FAK and paxillin, two potential targets in pancreatic cancer
TL;DR: Evidence in support of FAK as a potential therapeutic target is reviewed, related combinatorial therapies are summarized and Paxillin, an intracellular adaptor protein, connects integrins to FAK and plays a key role in assembly and disassembly of focal adhesions are summarized.
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Defining the molecular pathology of pancreatic body and tail adenocarcinoma
Stephan Dreyer,Nigel B. Jamieson,Nigel B. Jamieson,Rosanna Upstill-Goddard,Peter Bailey,Colin J. McKay,Colin J. McKay,Andrew V. Biankin,Andrew V. Biankin,David K. Chang,David K. Chang +10 more
TL;DR: The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas.
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AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling
Bo Kong,Christoph W. Michalski,Xin Hong,Nataliya Valkovskaya,Simon Rieder,Ivane Abiatari,Sylvia Streit,Mert Erkan,Irene Esposito,Helmut Friess,J. Kleeff +10 more
TL;DR: PCR array analysis revealed that ZAG-induced epithelial transdifferentiation was accompanied by a series of concerted cellular events including a shift in the energy metabolism and prosurvival signals, indicating that epigenetically regulated ZAG is a novel tumor suppressor essential for maintaining an epithelial phenotype.
Journal ArticleDOI
Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition
Claudia Blattmann,Susanne Oertel,Volker Ehemann,Markus Thiemann,Peter E. Huber,Peter E. Huber,Marc Bischof,Olaf Witt,Olaf Witt,Hedwig E. Deubzer,Hedwig E. Deubzer,Andreas E. Kulozik,Jürgen Debus,Klaus J. Weber +13 more
TL;DR: Results show that HDACIs enhance radiation action in OS and RMS cell lines, and inhibition of DNA repair, as well as increased apoptosis induction after exposure toHDACIs, can be mechanisms of radiosensitization by HDACI.
Journal ArticleDOI
MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis
Jiujie Cui,Zhuqing Zhou,Haiyan Yang,Feng Jiao,Ning Li,Yong Gao,Liwei Wang,Jingde Chen,Ming Quan +8 more
TL;DR: It is demonstrated that MST1 suppressed the progression of PDAC cells at least partly through ROS-induced pyroptosis and revealed that M ST1 would be a potential prognostic and therapeutic target for PDAC.
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