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| 1 | Role of AXL in invasion and drug resistance of colon and breast cancer cells and its association with p53 alterations显示文摘AIM To characterize AXL receptor tyrosine kinase(AXL)expression in relationship to tumor protein P53(TP53gene,p53 protein)and its role in tumor invasion and response to therapy.METHODS We used 14 cell lines,including 3 isogenic pairs carrying mutant/knockout p53,to gain insight into the relationship between AXL and TP53.These included HCT116,HCT116.p53 mutant,RKO,and RKO.p53-/-lines(all from colon cancers)as well as breast cancer cell lines MCF7 and 1001(MCF7-p53 mutant clone).He La cell line was used as a positive control for epithelial to mesenchymal transition(EMT).AXL expression was determined by Western blotting using rabbit monoclonal antibody clone C89E7.AXL si RNA silencing was performed and followed by collagen invasion assay.Cell viability analysis using the sulforhodamine B assay and the invasion assay were performed after exposure to chemotherapeutic agents(doxorubicin for breast cancer cells;5FU or irinotecan for colon cancer cells).RESULTS We showed that the introduction of p53 mutations or knockout increased expression levels of AXL in isogenic cells compared to the matching p53 wild-type parental cells.Overall,we found a trend for correlation between the potential EMT candidate AXL,p53 alterations,and EMT markers in colorectal and breast cancers.The expression of AXL in RKO cells,a rare colon cancer cell line with inactive Wnt signaling,suggests that the AXL oncogene might provide an alternative genetic pathway for colorectal carcinogenesis in the absence of Wnt signaling activation and TP53 mutation.AXL silencing in the TP53 mutant isogenic cell lines 1001,HCT116.p53 mutant and RKO.P53-/-was>95%efficient and the silenced cells were less invasive compared to the parental TP53 wild-type cells.AXL silencing showed a subtle trend to restore colon cancer cell sensitivity to5FU or irinotecan.Importantly,AXL expressing cells developed more invasive potential after exposure to chemotherapy compared to the AXL-silenced cells.CONCLUSION AXL is influenced by p53 status and could cause the emergence of aggressive clones after exposure to chemotherapy.These findings could have applications in cancer management. | Wael M Abdel-Rahman Noura A Al-khayyal Vidhya A Nair S R Aravind Maha Saber-Ayad | 2017 | World Journal of Gastroenterology2017，23，19： | 7 |
| 2 | The domains of death:evolution ofthe apoptosis machinery显示文摘 | ARAVIND L DIXIT V M KOONIN E | 1999 | Trends Biochem Sci1999，24，： | 1 |
| 3 | Modulation of cadmium-induced oxidative stress in Ceratophyllum demersum by zinc involves ascorbate-glutathione cycle and glutathione metabolism显示文摘 | Aravind P Prasad M N V | 2005 | Plant Physiology Bio-Chemistry2005，43，： | 1 |
| 4 | Impaired miR-146a expression links subclinical inflammation and insulin resistance in type 2 diabetes 显示文摘 | Balasubramanyam M Aravind S Gokulakrishnan K | 2011 | Mol Cell Biochem2011，351，12： | 1 |
| 5 | Evaluation of antioxidant, antitumor and immunmodulatory properties of polysaccharide isolated from fruit rind of Punica granatum显示文摘 | Joseph M M Aravind S R Vargese S | 2011 | Mol Med Report2011，5，2： | 1 |
| 6 | Genome of the extremely radiation-resistant bacterium Deinococcus radiodurans viewed from the perspective of comparative genomics显示文摘 | Makarova K S Aravind L Wolf Y I Tatusov R L Minton K W Koonin E V Daly M J | 2001 | Microbiology and Molecular Biology Reviews2001，65，1： | 1 |
| 7 | Optimization of microwave-assisted transesterification of dry algal biomass using response surface methodology显示文摘 | Prafulla DP Veera GG Aravind M at al | 2011 | Bioresource Technology2011，102，12： | 1 |
| 8 | Impaired miR- 146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes显示文摘 | Balasubramanyam M Aravind S Gokulakrishnan K | 2011 | Mol Cell Biochem2011，351，12： | 1 |
| 9 | Effect of inulin soluble dietary fibre addition on technological, sensory, and structural properties of durum wheat spaghetti 显示文摘 | Nisha Aravind Mike J Sissons Christopher M Fellows | 2012 | Food Chemistry2012，132，2： | 1 |
| 10 | Zinc alleviates cadmium- inducedoxidative stress in Ceratophllum demersum L:afree floating freshwater macrophyte显示文摘 | Aravind P Prasad M N V | 2003 | Plant Physiol Biochem2003，，41： | 1 |
| 11 | Formation of Al2Cu and AICu intermetallics in Al (Cu) alloy matrix composites by reaction sintering显示文摘 | ARAVIND M | 2004 | Material Science and Engineering A 3802004，，： | 1 |
| 12 | Ter-dependent stress response systems: novel pathways related to metal sensing, production ofa nucleoside-like metabolite, and DNA-processing显示文摘 | Anantharaman V lyer L M Aravind L | 2012 | Mol Biosyst2012，8，31： | 1 |
| 13 | Formation of Mg2Ni nanofibres in a Mg-based metal matrix composite显示文摘 | MAN G YAU E M Y ARAVIND M | 2004 | Philosophical Magazine2004，84，35： | 1 |
| 14 | Apoptotic molecular machinery: Vastly increased complexity in vertebrates revealed by genome comparisons显示文摘 | Aravind L Dixit V M Koonin E V | 2001 | Science2001，291，： | 1 |
| 15 | Genome sequence of the radioresistant bacteriumDeinococcus radiodurans R显示文摘 | White O Eisen J A Heidelberg J F Hickey E K Peterson J D Dodson R J Haft D H Gwinn M L Nelson W C Richardson D L Moffat K S Qin H Jiang L Pamphile W Crosby M Shen M Vamathevan J J Lam P McDonald L Utterback T Zalewski C Makarova K S Aravind L Daly M J Minton K W Fleischmann R D Ketchum K A Nelson K E Salzberg S Smith H O Venter J C Fraser C M | 1999 | Science1999，286，5444： | 1 |
| 16 | Characterization of thermo-mechanical and long-term behaviors of multi-layered composite materials 显示文摘 | Anastasia M Aravind N Kamran A Khan Shannon W | 2006 | Composites Science and Technology2006，66，： | 1 |
| 17 | Evolutionary dynamics of prokaryotic transcriptional regulatory networks显示文摘 | Madan-Babu M Teichmann S A Aravind L | 2006 | J Mol Biol2006，358，2： | 1 |
| 18 | Structure and evo- lution of transcriptional regulatory networks 显示文摘 | Babu M M Luscombe N M Aravind L | 2004 | Curr Opin in Struc Biol2004，14，： | 1 |
| 19 | Interleaving-based cyclic delay diversity OFDM systems over spatially corre- lated channels 显示文摘 | Senthil B Aravind R Prabhu K M M | 2013 | Circuits Systems and Signal Pro- cessing2013，32，1： | 1 |
| 20 | Microdrive operational and non - operational shockand vibration testing 显示文摘 | BERT F ARAVIND N M FRANK E | 2007 | Microsyst Teehno/2007，13，810： | 1 |
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