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| 1 | Nexus of signaling and endocytosis in oncogenesis driven by non-small cell lung cancer-associated epidermal growth factor receptor mutants显示文摘Epidermal growth factor receptor(EGFR) controls a wide range of cellular processes, and aberrant EGFR signaling as a result of receptor overexpression and/or mutation occurs in many types of cancer. Tumor cells in non-small cell lung cancer(NSCLC) patients that harbor EGFR kinase domain mutations exhibit oncogene addiction to mutant EGFR, which confers high sensitivity to tyrosine kinase inhibitors(TKIs). As patients invariably develop resistance to TKIs, it is important to delineate the cell biological basis of mutant EGFR-induced cellular transformation since components of these pathways can serve as alternate therapeutic targets to preempt or overcome resistance. NSCLC-associated EGFR mutants are constitutively-active and induce ligandindependent transformation in nonmalignant cell lines. Emerging data suggest that a number of factors are critical for the mutant EGFR-dependent tumorigenicity, and bypassing the effects of TKIs on these pathways promotes drug resistance. For example, activation of downstream pathways such as Akt, Erk, STAT3 and Src is critical for mutant EGFR-mediated biological processes. It is now well-established that the potency and spatiotemporal features of cellular signaling by receptor tyrosine kinases such as EGFR, as well as the specific pathways activated, is determined by the nature of endocytic traffic pathways through which the active receptors traverse. Recent evidence indicates that NSCLCassociated mutant EGFRs exhibit altered endocytic trafficking and they exhibit reduced Cbl ubiquitin ligasemediated lysosomal downregulation. More recent work has shown that mutant EGFRs undergo ligand-independent traffic into the endocytic recycling compartment, a behavior that plays a key role in Src pathway activation and oncogenesis. These studies are beginning to delineate the close nexus between signaling and endocytic traffic of EGFR mutants as a key driver of oncogenicprocesses. Therefore, in this review, we will discuss the links between mutant EGFR signaling and endocytic properties, and introduce potential mechanisms by which altered endocytic properties of mutant EGFRs may alter signaling and vice versa as well as their implications for NSCLC therapy. | Byung Min Chung Eric Tom Neha Zutshi Timothy Alan Bielecki Vimla Band Hamid Band | 2014 | World Journal of Clinical Oncology2014，5，5： | 3 |
| 2 | Maximisation of signal-to-noise ratio in infrared radiation receivers 显示文摘 | Z Bielecki | 2002 | Opto-Electronics Review2002，10，3： | 1 |
| 3 | Intraosseous and intra discal gas in association with spinal infection: report of three cases显示文摘 | Bielecki DK Sartoris D Resnick D | 1986 | AJR Am J Roentgenol1986，147，1： | 1 |
| 4 | Origin of terraced hillslopes on active folds in the southern San Joaquin Valley, California 显示文摘 | Bielecki A E Muel|er K J | 2002 | Geomorphology2002，42，： | 1 |
| 5 | Benefit of percutaneous in- jection of autologous platelet-leukocyte-rich gel in patients with de- layed union and nonunion显示文摘 | Bielecki T Gazdzik TS Szczepanski T | 2008 | Eur Surg Res2008，40，： | 1 |
| 6 | Malignant trans-formation in inflammatory bowel disease-surveillanceguide显示文摘 | Stallmach A Bielecki C Schmidt C | 2009 | Dig Dis2009，27，4： | 1 |
| 7 | Cavity ring down spectroscopy: Detection of trace amounts of substance显示文摘 | Stacewicz T Wojtas J Bielecki Z Nowakowski M Mikolajczyk J Medrzycki R Rutecka B | 2012 | Opto-Electronics Review2012，20，1： | 1 |
| 8 | Isolation and properties of Aspergillus niger IBT-90 xylanase for bakery显示文摘 | Romanowska I Polak J Bielecki S | | 0，，06： | 1 |
| 9 | Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leuko- cyte-and platelet-rich fibrin (L-PRF)显示文摘 | Dohan Ehrenfest DM Bielecki T Jimbo R | 2012 | Curr Pharm Biotechnol2012，13，7： | 1 |
| 10 | Influence of Some New Aminophosphonates on Electrical Properties and Stability of Plasma Membranes of Plant Cells显示文摘 | SARAPUK J BIELECKI K TRELA Z | 2002 | Acta Soc Bot Pol2002，71，3： | 1 |
| 11 | Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study显示文摘 | Bielecki TM Gazdzik TS Arendt J Szczepanski T Krol W Wielkoszynski T | 2007 | J Bone Joint Surg Br2007，89，3： | 1 |
| 12 | The effect of prophylactic doses of nadroparin and therapeutic doses of betamethasone on skin flap survival in rats 显示文摘 | Bielecki M Karpik M Skowroflski J | 2009 | Folia Histochem Cytobiol2009，47，4： | 1 |
| 13 | Trauma care for the year2000显示文摘 | Bielecki K | 2000 | Przegl-Lek2000，575，： | 1 |
| 14 | Correlations between two markers of sperm DNA integrity,DNA denaturation and DNA fragmentation,in fertile and infertile men显示文摘 | Zini A Bielecki R Phang D | 2001 | Fertil Steril2001，75，4： | 1 |
| 15 | High serumsCDl 63 / sTWEAK ratio is associated with lower risk of digitalulcers but more severe skin disease in patients with systemicsclerosis显示文摘 | Kowal-Bielecka O Bielecki M Guiducci S etal | 2013 | Arthritis Res Ther2013，15，3： | 1 |
| 16 | Recurrent ileostomy prolapse: is it a solved problem?显示文摘 | K. Bielecki | 2010 | Techniques in Coloproctology2010，，3： | 1 |
| 17 | Large bowel perforation:morbidity and mortality显示文摘 | Bielecki Kaminski P Klukowski M | 2002 | Tech Coloproctol2002，6，3： | 1 |
| 18 | Life estimation for long rod composite insulators subjected to accelerating aging by combined static and cyclic loading 显示文摘 | WANKOWICZ J G BIELECKI J | 2011 | IEEE Transactions on Dielectrics and Electrical Insulation2011，18，1： | 1 |
| 19 | Spontaneous bacterial peritonitis with Streptococcus constellatus in an HIV positive patient显示文摘 | Bielecki JW Gsteiger C Briner V | 2000 | Schweiz Med Wochenschr2000，130，3： | 1 |
| 20 | Large bowel perforation : mor- bidity and mortality显示文摘 | Bielecki K Kamifiski P Klukowski M | 2002 | Tech Coloproctol2002，6，3： | 1 |
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