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Novel mutations involving βI-, βIIA-, or βIVB-tubulin isotypes with functional resemblance to βIII-tubulin in breast cancer

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Abstract

Tubulin is the target for very widely used anti-tumor drugs, including Vinca alkaloids, taxanes, and epothilones, which are an important component of chemotherapy in breast cancer and other malignancies. Paclitaxel and other tubulin-targeting drugs bind to the β subunit of tubulin, which is a heterodimer of α and β subunits. β-Tubulin exists in the form of multiple isotypes, which are differentially expressed in normal and neoplastic cells and differ in their ability to bind to drugs. Among them, the βIII isotype is overexpressed in many aggressive and metastatic cancers and may serve as a prognostic marker in certain types of cancer. The underpinning mechanisms accounting for the overexpression of this isotype in cancer cells are unclear. To better understand the role of β-tubulin isotypes in cancer, we analyzed over 1000 clones from 90 breast cancer patients, sequencing their β-tubulin isotypes, in search of novel mutations. We have elucidated two putative emerging molecular subgroups of invasive breast cancer, each of which involve mutations in the βI-, βIIA-, or βIVB isotypes of tubulin that increase their structural, and possibly functional, resemblance to the βIII isotype. A unifying feature of the first of the two subgroups is the mutation of the highly reactive C239 residue of βI- or βIVB-tubulin to L239, R239, Y239, or P239, culminating in probable conversion of these isotypes from ROS-sensitive to ROS-resistant species. In the second subgroup, βI, βIIA, and βIVB have up to seven mutations to the corresponding residues in βIII-tubulin. Given that βIII-tubulin has emerged as a pro-survival factor, overexpression of this isotype may confer survival advantages to certain cancer cell types. In this mini-review, we bring attention to a novel mechanism by which cancer cells may undergo adaptive mutational changes involving alternate β-tubulin isotypes to make them acquire some of the pro-survival properties of βIII-tubulin. These “hybrid” tubulins, combining the sequences and/or properties of two wild-type tubulins (βIII and either βI, βIIA, or βIVB), are novel isotypes expressed solely in cancer cells and may contribute to the molecular understanding and stratification of invasive breast cancer and provide novel molecular targets for rational drug development.

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References

  • Amos LA, Löwe (1999) How taxol® stabilizes microtubule structure. Chemistry & Biology 6:R65–R69

    Article  CAS  Google Scholar 

  • Anders KR, Botstein D (2001) Dominant-lethal α-tubulin mutants defective in microtubule depolymerization in yeast. Mol Biol Cell 12:3973–3986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bai R, Lin CM, Nguyen NY, Liu TY, Hamel E (1989) Identification of the cysteine residue of β-tubulin alkylated by the antimitotic agent 2,4-dichlorobenzyl thiocyanate, facilitated by separation of the protein subunits of tubulin by hydrophobic column chromatography. Biochemistry 28:5606–5612

    Article  CAS  PubMed  Google Scholar 

  • Bai R, Covell DG, Pei XF, Ewell JB, Nguyen NY, Brossi A, Hamel E (2000) Mapping the binding site of colchicinoids on β-tubulin: 2-Chloroacetyl-2-demethylthiocolchicine covalently reacts predominantly with cysteine 239 and secondarily with cysteine 354. J Biol Chem 275:40443–40452

    Article  CAS  PubMed  Google Scholar 

  • Banerjee A, Ludueña RF (1992) Kinetics of colchicine binding to purified β-tubulin isotypes from bovine brain. J Biol Chem 267:13335–13339

    CAS  PubMed  Google Scholar 

  • Banerjee A, D’Hoore A, Engelborghs Y (1994) Interaction of desacetamidocolchicine, a fast-binding analogue of colchicine, with isotypically pure tubulin dimers αβII, αβIII, and αβIV. J Biol Chem 269:10324–10329

    CAS  PubMed  Google Scholar 

  • Banerjee A, Engelborghs Y, D’Hoore A, Fitzgerald TJ (1997) Interactions of a bicyclic analog of colchicine with β-tubulin isoforms αβII, αβIII and αβIV. Eur J Biochem 246:420–424

    Article  CAS  PubMed  Google Scholar 

  • Bastani M, Vos L, Asgarian N, Deschenes J, Graham K, Mackey J, Greiner R (2013) A machine learned classifier that uses gene expression data to accurately predict estrogen receptor status. PLoS One 8:e82144

    Article  PubMed  PubMed Central  Google Scholar 

  • Bowne-Anderson H, Zanic M, Kauer M, Howard J (2013) Microtubule dynamic instability: a new model with coupled GTP hydrolysis and multistep catastrophe. BioEssays 35:452–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown NS, Bicknell R (2001) Hypoxia and oxidative stress in breast cancer: oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res 3:323–327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bustin SA, Benes V, Garson JA et al (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622

    Article  CAS  PubMed  Google Scholar 

  • Churchill CDM, Klobukowski M, Tuszynski JA (2015) The unique binding mode of laulimalide to two tubulin protofilaments. Chem Biol Drug Des 86:190–199

    Article  CAS  PubMed  Google Scholar 

  • De Donato M, Mariani M, Petrella L et al (2012) Class III beta-tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer. J Cell Physiol 227:1034–1041

    Article  CAS  PubMed  Google Scholar 

  • Derry WB, Wilson L, Khan IA, Ludueña RF, Jordan MA (1997) Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified β tubulin isotypes. Biochemistry 36:3554–3562

    Article  CAS  PubMed  Google Scholar 

  • Dong Z, Thoma RS, Crimmins DL, McCourt DW, Tuley EA, Sadler JE (1994) Disulfide bonds required to assemble functional von Willebrand factor multimers. J Biol Chem 260:6753–6758

    Google Scholar 

  • Dráberová E, Lukás Z, Ivanyi D, Viklický V, Dráber P (1998) Expression of class III β-tubulin in normal and neoplastic human tissues. Histochem Cell Biol 109:231–239

    Article  PubMed  Google Scholar 

  • Dráberová E, Del Valle L, Gordon J et al (2008) Class III β-tubulin is constitutively co-expressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: implications for phenotypic identity. J Neuropathol Exp Neurol 67:341–354

    Article  PubMed  Google Scholar 

  • Dustin P (1984) Microtubules. Springer-Verlag, Berlin

  • Dumontet C, Jordan MA, Lee F FY, Dumontet C, MA Jordan, Lee F FY, (2009) Ixabepilone: targeting  IIItubulin expression in taxane-resistant malignancies. Molecular Cancer Therapeutics 8 (1):17–25

  • Dumontet C, Jordan MA (2010) Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 9:790–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egevad L, Valdman A, Wiklund NP, Sève P, Dumontet C (2010) Beta-tubulin III expression in prostate cancer. Scand J Urol Nephrol 44:371–377

    Article  CAS  PubMed  Google Scholar 

  • Ewing B, Green P (1998) Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res 8:186–194

    Article  CAS  PubMed  Google Scholar 

  • Ewing B, Hillier L, Wendl MC, Green P (1998) Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8:175–185

    Article  CAS  PubMed  Google Scholar 

  • Ferrandina G, Zannoni GF, Martinelli E et al (2006) Class III β-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res 12:2774–2779

    Article  CAS  PubMed  Google Scholar 

  • Ferrandina G, Martinelli E, Zannoni GF, Distefano M, Paglia A, Ferlini C, Scambia G (2007) Expression of class III β-tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome. Gynecol Oncol 104:326–330

    Article  CAS  PubMed  Google Scholar 

  • Gan PP, Pasquier E, Kavallaris M (2007) Class III β-tubulin mediates sensitivity to chemotherapeutic drugs in non-small cell lung cancer. Cancer Res 67:9356–9363

    Article  CAS  PubMed  Google Scholar 

  • Garland DL (1978) Kinetics and mechanism of colchicine binding to tubulin: evidence for ligand-induced conformational change. Biochemistry 17:4266–4272

    Article  CAS  PubMed  Google Scholar 

  • Gigant Benoît, Wang Chunguang, Ravelli Raimond B G, Roussi Fanny, Steinmetz O, Curmi Patrick A, Sobel André, Knossow Marcel, Gigant Benoît, Wang Chunguang, Ravelli Raimond B G, Roussi Fanny, Steinmetz Michel O, Curmi Patrick A. Sobel André, Knossow Marcel (2005) Structural basis for the regulation of tubulin by vinblastine. Nature 435 (7041):519–522

  • Goldspiel BR (1997) Clinical overview of the taxanes. Pharmacotherapy 17:110S–125S

  • Gordon D (2004) Viewing and editing assembled sequences using Consed. In: Baxevanis AD, Davison DB (eds) Current protocols in bioinformatics. Wiley, New York, pp. 11.2.1–11.2.43

    Google Scholar 

  • Gordon D, Abajian C, Green P (1998) Consed: a graphical tool for sequence finishing. Genome Res 8:195–202

    Article  CAS  PubMed  Google Scholar 

  • Gordon D, Desmarais C, Green P (2001) Automated finishing with Autofinish. Genome Res 11:614–625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green MR, Sambrook J (2012) Cloning and transformation with plasmid vectors. In: Green MR, Sambrook J (eds) Molecular cloning: a laboratory manual, 4th edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 157–260

    Google Scholar 

  • Herbert C, Jacquet C, Borel C, Esquerre-Tugave MT, Dumas B (2002) A cis-acting sequence homologous to the yeast filamentation and invasion response element regulates expression of a pectinase gene from the bean pathogen Colletotrichum lindemuthianum. J Biol Chem 277:29125–12131

    Article  CAS  PubMed  Google Scholar 

  • Huzil JT, Winter P, Johnson L et al (2010) Computational design and biological testing of highly cytotoxic colchicine ring a modifications. Chem Biol Drug Design 75:541–550

    Article  CAS  Google Scholar 

  • Jordan MA, Wilson L (1998) Microtubules and actin filaments: dynamic targets for cancer chemotherapy. Curr Opin Cell Biol 10:123–130

    Article  CAS  PubMed  Google Scholar 

  • Karki R, Mariani M, Andreo IM, He S, Scambia G, Shahabi S, Ferlini C (2013) βIII-tubulin: biomarker of taxane resistance or drug target? Expert Opin Ther Targets 17:461–472

    Article  CAS  PubMed  Google Scholar 

  • Katsetos CD, Dráber P (2012) Tubulins as therapeutic targets in cancer: from bench to bedside. Curr Pharm Des 18:2778–2792

    Article  CAS  PubMed  Google Scholar 

  • Katsetos CD, Frankfurter A, Christakos S, Mancall EL, Vlachos I, Urich H (1993) Differential localization of class III β-tubulin isotype and calbindin-D28k defines distinct neuronal types in the developing human cerebellar cortex. J Neuropathol Exp Neurol 52:655–666

    Article  CAS  PubMed  Google Scholar 

  • Katsetos CD, Karkavelas G, Herman MM, Vinores SA, Provencio J, Spano AJ, Frankfurter A (1998) Class β-tubulin isotype (βIII) in the adrenal medulla: I. Localization in the developing human adrenal medulla. Anat Rec 250:335–343

    Article  CAS  PubMed  Google Scholar 

  • Katsetos CD, Legido A, Perentes E, Mörk SJ (2003a) Class III β-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology. J Child Neurol 18:851–866

    Article  PubMed  Google Scholar 

  • Katsetos CD, Herman MM, Mörk SJ (2003b) Class III β-tubulin in human development and cancer. Cell Motil Cytoskeleton 55:77–96

    Article  CAS  PubMed  Google Scholar 

  • Katsetos CD, Dráberová E, Legido A, Dumontet C, Dráber P (2009) Tubulin targets in the pathobiology and therapy of glioblastoma multiforme. I Class III β-tubulin J Cell Physiol 2221:505–513

    Google Scholar 

  • Katsetos CD, Dráber P, Kavallaris M (2011) Targeting βIII-tubulin in glioblastoma multiforme: from cell biology and histopathology to cancer therapeutics. Anti Cancer Agents Med Chem 11:719–728

    Article  CAS  Google Scholar 

  • Katsetos CD, Reginato MJ, Baas PW et al (2015) Emerging microtubule targets in glioma therapy. Semin Pediatr Neurol 22:49–72

    Article  PubMed  Google Scholar 

  • Kavallaris M (2010) Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer 10:194–204

    Article  CAS  PubMed  Google Scholar 

  • Khan IA, Ludueña RF (1996) Phosphorylation of βIII-tubulin. Biochemistry 35:3704–3711

    Article  CAS  PubMed  Google Scholar 

  • Khan IA, Ludueña RF (2003) Different effects of vinblastine on the polymerization of isotypically purified tubulins from bovine brain. Investig New Drugs 21:3–13

    Article  CAS  Google Scholar 

  • Leandro-García LJ, Leskelä S, Landa I et al (2010) Tumoral and tissue-specific expression of the major human β-tubulin isotypes. Cytoskeleton 67:214–223

    Article  PubMed  Google Scholar 

  • Lek M, Karczewski KJ, Minikel EV et al (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285–291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levallet G, Bergot E, Antoine M et al (2012) Intergroupe francophone de Cancérologie Thoracique (IFCT): high TUBB3 expression, an independent prognostic marker in patients with early non-small cell lung cancer treated by preoperative chemotherapy, is regulated by K-Ras signaling pathway. Mol Cancer Ther 11:1203–1213

    Article  CAS  PubMed  Google Scholar 

  • Little M, Ludueña RF (1985) Structural differences between β1- and β2-tubulins: implications for microtubule assembly and colchicine binding. EMBO J 4:51–56

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Van Eck J, Cong B, Tanksley SD (2002) A new class of regulatory genes underlying the cause of pear-shaped tomato fruit. Proc Natl Acad Sci U S A 99:13302–13306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopata MA, Cleveland DW (1987) In vivo microtubules are copolymers of available β-tubulin isotypes: localization of each of six vertebrate β-tubulin isotypes using polyclonal antibodies elicited by synthetic peptide antigens. J Cell Biol 105:1707–1720

    Article  CAS  PubMed  Google Scholar 

  • Löwe J, Li H, Downing KH, Nogales E (2001) Refined structure of αβ-tubulin at 3.5 Å resolution. J Mol Biol 313:1045–1047

    Article  PubMed  Google Scholar 

  • Lu Q, Moore GD, Walss C, Ludueña RF (1998) Structural and functional properties of tubulin isotypes. Adv Struct Biol 5:203–227

    Article  CAS  Google Scholar 

  • Luchko T, Huzil JT, Stepanova M, Tuszynski J (2008) Conformational analysis of the carboxy-terminal tails of human β-tubulin isotypes. Biophys J 94:1971–1982

    Article  CAS  PubMed  Google Scholar 

  • Ludueña RF (1998) The multiple forms of tubulin: different gene products and covalent modifications. Int Rev Cytol 178:207–275

    Article  PubMed  Google Scholar 

  • Ludueña RF, Roach MC, Trcka PP, Little M, Palanivelu P, Binkley P, Prasad V (1982) β2-tubulin, a form of chordate brain tubulin with lesser reactivity toward an assembly-inhibiting sulfhydryl directed cross-linking reagent. Biochemistry 21:4787–4794

    Article  PubMed  Google Scholar 

  • Mariani M, Karki R, Spennato M, Pandya D, He S, Andreoli M, Fiedler P, Ferlini C (2015) Class III β-tubulin in normal and cancer tissues. Gene 563:109–114

    Article  CAS  PubMed  Google Scholar 

  • Mayadas TN, Wagner DD (1992) Vicinal cysteines in the prosequence play a role in von Willebrand multimer assembly. Proc Natl Acad Sci U S A 89:3531–3535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCarroll JA, Gan PP, Liu M, Kavallaris M (2010) βIII-tubulin is a multifunctional protein involved in drug sensitivity and tumorigenesis in non-small cell lung cancer. Cancer Res 70:4995–5003

    Article  CAS  PubMed  Google Scholar 

  • McCarroll JA, Gan PP, Erlich RB et al (2015) TUBB3/βIII-tubulin acts through the PTEN/AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer. Cancer Res 75:415–425

    Article  CAS  PubMed  Google Scholar 

  • Minotti G, Cairo G, Monti E (1999) Role of iron in anthracycline cardiotoxicity: new tunes for an old song? FASEB J 13:199–212

    CAS  PubMed  Google Scholar 

  • Mitchison T, Kirschner M (1984) Dynamic instability of microtubule growth. Nature 312:237–242

    Article  CAS  PubMed  Google Scholar 

  • Mooberry SL, Tien G, Hernandez AH, Plubrukarn A, Davidson BS (1999) Laulimalide and isolaulilamide: new paclitaxel-like microtubule-stabilizing agents. Cancer Res 59:653–660

    CAS  PubMed  Google Scholar 

  • Müller-Reichert T, Chrétien D, Severin F, Hyman AA (1998) Structural changes at microtubule ends accompanying GTP hydrolysis: information from a slowly hydrolyzable analogue of GTP, guanylyl(α,β)methylenediphosphonate. Proc Natl Acad Sci U S A 95:3661–3666

    Article  PubMed  PubMed Central  Google Scholar 

  • Nicolini A, Giardino R, Carpi A, Ferrari P, Anselmi L, Colosimo S, Conte M, Fini M, Giavaresi G, Berti P, Miccoli P, Nicolini A, Giardino R, Carpi A, Ferrari P, Anselmi L, Colosimo S, Conte M, Fini M, Giavaresi G, Berti P, Miccoli P (2006) Metastatic breast cancer: an updating. Biomedicine & Pharmacotherapy 60 (9):548–556

  • Nogales E, Wolf SG, Khan IA, Ludueña RF, Downing KH (1995) Structure of tubulin at 6.5 Å and location of the taxol-binding site. Nature 375:424–427

  • Palanivelu P, Ludueña RF (1982) Interaction of the τ-tubulin vinblastine complex with colchicine, podophyllotoxin and N,N′-ethylene bis(iodoacetamide). J Biol Chem 257:6311–6315

    CAS  PubMed  Google Scholar 

  • Pamula MC, Ti SC, Kapoor TM (2016) The structured core of human β tubulin confers isotype-specific polymerization properties. J Cell Biol 213:425–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panda D, Miller HP, Banerjee A, Ludueña RF, Wilson L (1994) Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci U S A 91:11358–11362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parker AL, Kavallaris M, McCarroll JA (2014) Microtubules and their role in cellular stress in cancer. Front Oncol 4:153

    Article  PubMed  PubMed Central  Google Scholar 

  • Pryor DE, O’Brate A, Bilcer G, Diaz JF, Wang Y, Wang Y, Kabaki M, Jung MK, Andreu JM, Ghosh AK, Giannakakou P, Hamel E (2002) The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry 41:9109–9115

    Article  CAS  PubMed  Google Scholar 

  • Punnonen K, Ahotupa M, Asiashi K, Hyöty M, Kudo R, Punnonen R (1994) Antioxidant enzyme activities and oxidative stress in human breast cancer. J Cancer Res Clin Oncol 120:374–377

    Article  CAS  PubMed  Google Scholar 

  • Raspaglio G, Filippetti F, Prislei S, Penci R, De Maria I, Cicchillitti L, Mozzetti S, Scambia G, Ferlini C (2008) Hypoxia induces class III β-tubulin gene expression by HIF-1α binding to its 3′ flanking region. Gene 409:100–108

    Article  CAS  PubMed  Google Scholar 

  • Ravelli Raimond BG, Gigant Benoît, Curmi Patrick A, Jourdain Isabelle, Lachkar Sylvie, Sobel André, Knossow Marcel, Ravelli Raimond BG, Gigant Benoît, Curmi Patrick A, Jourdain Isabelle, Lachkar Sylvie, Sobel André, Knossow Marcel (2004) Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428 (6979):198–202

  • Ray G, Batra S, Shukla NK, Deo S, Raina V, Ashok S, Husain SA (2000) Lipid peroxidation, free radical production and antioxidant status in breast cancer. Breast Cancer Res & Treatment 59:163–170

    Article  CAS  Google Scholar 

  • Sartorelli AC, Creasey WA (1969) Cancer chemotherapy. Ann. Rev. Pharmacol. 9:51–72

  • Schwarz PM, Liggins JR, Ludueña RF (1998) β-tubulin isotypes purified from bovine brain have different relative stabilities. Biochemistry 37:4687–4692

    Article  CAS  PubMed  Google Scholar 

  • Sève P, Dumontet C (2008) Is class III β-tubulin a predictive factor in patients receiving tubulin-binding agents? Lancet Oncol 9:168–175

    Article  PubMed  Google Scholar 

  • Sharma J, Ludueña RF (1994) Use of N,N′-polymethylenebis(iodoacetamide) derivatives as probes for the detection of conformational differences in tubulin isotypes. J Prot Chem 13:165–176

    Article  CAS  Google Scholar 

  • Shelden E, Wadsworth P (1993) Observation and quantification of individual microtubule behavior in vivo: microtubule dynamics are cell-type specific. J Cell Biol 120:935–945

    Article  CAS  PubMed  Google Scholar 

  • Snyder JP, Nettles JH, Cornett B, Downing KH, Nogales E (2001) The binding conformation of taxol in β-tubulin: a model based on electron crystallographic density. Proc Nat Acad Sci USA 98:5312–5316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Terry S, Ploussard G, Allory Y et al (2009) Increased expression of class III β-tubulin in castration-resistant human prostate cancer. Br J Cancer 101:951–856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tseng CY, Mane JY, Winter P, Johnson L, Huzil T, Izbicka E, Luduena RF, Tuszynski JA (2010) Quantitative analysis of the effect of tubulin isotype expression on sensitivity of cancer cell lines to a set of novel colchicine derivatives. Molec Cancer 9:131–149

    Article  Google Scholar 

  • Tsourlakis MC, Weigand P, Grupp K et al (2014) βIII-tubulin overexpression is an independent predictor of prostate cancer progression tightly linked to ERG fusion status and PTEN deletion. Am J Pathol 184:609–617

    Article  CAS  PubMed  Google Scholar 

  • Vásquez-Vivar J, Martasek P, Hogg N, Masters BC, Pritchard KA Jr, Kalyanaraman B (1997) Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry 36:11293–11297

    Article  PubMed  Google Scholar 

  • Wilmes A, O’Sullivan D, Chan A, Chandrahasen C, Paterson I, Northcote PT, Flamme ACL, Miller JH (2011) Synergistic interactions between peloruside a and other microtubule-stabilizing and destabilizing agents in cultured human ovarian carcinoma cells and murine T cells. Can Chem Pharma 68:117–126

    Article  CAS  Google Scholar 

  • Xu K, Schwarz PM, Ludueña RF (2002) The interaction of nocodazole with tubulin isotypes. Drug Devel Res 55:91–96

    Article  CAS  Google Scholar 

  • Yeh LCC, Banerjee A, Prasad V et al (2016) Effect of CH-35, a novel anti-tumor colchicine analogue, on breast cancer cells overexpressing the βIII isotype of tubulin. Investig New Drugs 34:129–137

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Drs. Anna Portyanko, Veronica Contreras-Shannon, Stephen Hardies, and Pavel Dráber for their encouragement and stimulating conversations. CDK acknowledges support for his research received from the Commonwealth Universal Research Enhancement (CURE) Program. JAT acknowledges support for his research received from the Allard Foundation and the Alberta Cancer Foundation. Tubulin sequences were generated with support from Alberta Innovates Technology Futures (AITF), Innovates Centers of Research Excellence (iCORE), and the Musea Ventures (all to GKSW). RFL owns shares in the OncoVista Innovative Therapies, Inc. (14785 Omicron Dr. # 104, San Antonio, TX 78245).

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Authors and Affiliations

  1. Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada

    Weiwei Wang, Jordan Patterson & Gane Ka-Shu Wong

  2. Beijing Institute of Genomics, Key Laboratory of Genome Sciences and Information, Chinese Academy of Sciences, Beijing, 100101, China

    Hangxiao Zhang & Xumin Wang

  3. Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada

    Philip Winter, Kathryn Graham, Sunita Ghosh, John R. Mackey & Jack A. Tuszynski

  4. Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

    John C. Lee & Richard F. Ludueña

  5. Department of Pediatrics, St. Christopher’s Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, 19134, USA

    Christos D. Katsetos

  6. Department of Pathology and Laboratory Medicine, St. Christopher’s Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, 19134, USA

    Christos D. Katsetos

  7. Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9, Canada

    Gane Ka-Shu Wong

  8. BGI-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China

    Gane Ka-Shu Wong

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  1. Weiwei Wang
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  3. Xumin Wang
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  7. Sunita Ghosh
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  9. Christos D. Katsetos
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  13. Richard F. Ludueña
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Correspondence to Richard F. Ludueña.

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This study was conducted after approval of the local institutional ethics review (Local Ethics number 25481; Genetic sequencing for β-tubulin mutations in taxane pretreated breast cancer).

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Richard F. Luduena owns shares in the OncoVista Innovative Technologies, San Antonio, TX. Otherwise, there are no conflicts of interest.

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Wang, W., Zhang, H., Wang, X. et al. Novel mutations involving βI-, βIIA-, or βIVB-tubulin isotypes with functional resemblance to βIII-tubulin in breast cancer. Protoplasma 254, 1163–1173 (2017). https://doi.org/10.1007/s00709-016-1060-1

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