scholarly journals Abstract 5780: 3Dex-vivoassay platform using primary lung cancer cells in malignant pleural effusions as predictor for clinical outcome of personalized chemotherapy

Author(s):  
Cheng-guang Wu ◽  
Francesca Chiovaro ◽  
Tamara Tanos ◽  
Alex Soltermann ◽  
Sumeer Dhar
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Onsurang Wattanathamsan ◽  
Rawikorn Thararattanobon ◽  
Ratchanee Rodsiri ◽  
Pithi Chanvorachote ◽  
Chanida Vinayanuwattikun ◽  
...  

AbstractThe posttranslational modifications (PTMs) of microtubules have been reported to play an important role in cancer aggressiveness, including apoptosis resistance. In this study, we aimed to investigate the biological role of microtubule PTMs in the regulation of paclitaxel responsiveness. The acetylated tubulin (Ace-tub) level was strongly associated with paclitaxel sensitivity, as observed in patient-derived primary lung cancer cells and xenografted immunodeficient mice. We showed that paclitaxel-resistant H460 lung cancer cells, generated by a stepwise increase in paclitaxel, exhibited markedly increased tubulin acetylation and consequently acquired paclitaxel resistance. Upregulation of tubulin acetylation by overexpression of α-tubulin acetyltransferase 1 wild-type (αTAT1wt), an enzyme required for acetylation, or by treatment with trichostatin A (TSA), a histone deacetylase 6 (HDAC6) inhibitor, significantly attenuated paclitaxel-induced apoptosis. Investigation of the underlying mechanism revealed that the levels of antiapoptotic Mcl-1 appeared to increase in αTAT1wt-overexpressing and TSA-treated cells compared to control cells, whereas the levels of other antiapoptotic regulatory proteins were unchanged. On the other hand, decreased tubulin acetylation by αTAT1 RNA interference downregulated Mcl-1 expression in patient-derived primary lung cancer and paclitaxel-resistant lung cancer cells. A microtubule sedimentation assay demonstrated that Mcl-1 binds to microtubules preferentially at Ace-type, which prolongs the Mcl-1 half-life (T1/2). Furthermore, immunoprecipitation analysis revealed that polyubiquitination of Mcl-1 was extensively decreased in response to TSA treatment. These data indicate that tubulin acetylation enhances the resistance to paclitaxel-induced cell death by stabilizing Mcl-1 and protecting it from ubiquitin–proteasome-mediated degradation.


Oncology ◽  
2016 ◽  
Vol 90 (5) ◽  
pp. 280-288 ◽  
Author(s):  
Martina Puglisi ◽  
Adam Stewart ◽  
Parames Thavasu ◽  
Michael Frow ◽  
Suzanne Carreira ◽  
...  

2017 ◽  
Vol 31 (20) ◽  
pp. 2099-2112 ◽  
Author(s):  
Shuan Rao ◽  
Verena Sigl ◽  
Reiner Alois Wimmer ◽  
Maria Novatchkova ◽  
Alexander Jais ◽  
...  

Haigan ◽  
1987 ◽  
Vol 27 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Hiroshi Isobe ◽  
Masami Ito ◽  
Toru Shimizu ◽  
Hirotoshi Dosaka ◽  
Yoshikazu Araya ◽  
...  

2013 ◽  
Vol 35 (8) ◽  
pp. 1165-1174 ◽  
Author(s):  
Joseph Seo ◽  
Soon-Jung Park ◽  
Jhingook Kim ◽  
So-Jung Choi ◽  
Sung-Hwan Moon ◽  
...  

2014 ◽  
Vol 32 (7) ◽  
pp. 339-348 ◽  
Author(s):  
Nupur N. Gangopadhyay ◽  
James D. Luketich ◽  
Amy Opest ◽  
Rodney Landreneau ◽  
Matthew J. Schuchert

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