title: Modulation of septin and molecular motor recruitment in the microtubule environment of the Taxol-resistant human breast cancer cell line MDA-MB-231.
abstract: Cell resistance to low doses of paclitaxel (Taxol) involves a modulation of microtubule (MT) dynamics. We applied a proteomic approach based on 2-DE coupled with MS to identify changes in the MT environment of Taxol-resistant breast cancer cells. Having established a proteomic pattern of the microtubular proteins extracted from MDA-MB-231 cells, we verified by Western blotting that in resistant cells, α- and β-tubulins (more specifically the βIII and βIV isotypes) increased. Interestingly, four septins (SEPT2, 8, 9 and 11), which are GTPases involved in cytokinesis and in MT/actin cytoskeleton organization, were overexpressed and enriched in the MT environment of Taxol-resistant cells compared to their sensitive counterpart. Changes in the MT proteome of resistant cells also comprised increased kinesin-1 heavy chain expression and recruitment on MTs while dynein light chain-1 was downregulated. Modulation of motor protein recruitment around MTs might reflect their important role in controlling MT dynamics via the organization of signaling pathways. The identification of proteins previously unknown to be linked to taxane-resistance could also be valuable to identify new biological markers of resistance.
authors.affiliation: Faculté de Pharmacie, Univ. Paris-Sud, 5 rue Jean-Baptiste Clément, Châtenay-Malabry, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Froidevaux-Klipfel
authors.forename: Florence
authors.initials: F
authors.lastname: Poirier
authors.forename: Céline
authors.initials: C
authors.lastname: Boursier
authors.forename: Ronan
authors.initials: R
authors.lastname: Crépin
authors.forename: Christian
authors.initials: C
authors.lastname: Poüs
authors.forename: Bruno
authors.initials: B
authors.lastname: Baudin
authors.forename: Anita
authors.initials: A
authors.lastname: Baillet
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D058112:Septins / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020543:Proteome; D014404:Tubulin; D050257:Tubulin Modulators; D058112:Septins; D017239:Paclitaxel