SEPT9_V1 protein expression is associated with human cancer cell resistance to microtubule-disrupting agents.
SEPT9 is a mammalian septin family member. There is growing evidence that SEPT9 plays a role in cancer. The protein product, SEPT9_V1, associates with microtubules and interacts with hypoxia-inducible factor (HIF)-1alpha, the regulated subunit of the key transcription factor HIF-1. HIF-1 transcriptional activity is thoroughly dependent on intact microtubules. We tested the hypothesis that SEPT9_V1 confers resistance to microtubule-mediated HIF-1 inhibitors. SEPT9_V1 protein expression was strongly correlated with susceptibility of a wide range of cancer cells to 2-methoxyestradiol and paclitaxel. Our results revealed that SEPT9_V1 could serve as a biomarker for therapeutic resistance to microtubule disrupting agents.
Amir
Sharon
S
Prostate Cancer Research Laboratory, Department of Urology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Mabjeesh
Nicola J
NJ
D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D007191:Indazoles / Q000494:pharmacology; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017239:Paclitaxel / Q000494:pharmacology*; D020033:Protein Isoforms; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D058112:Septins; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D050257:Tubulin Modulators / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016227:Benzoquinones; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D047029:Lactams, Macrocyclic; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D050257:Tubulin Modulators; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; C112765:tanespimycin; D004958:Estradiol; D000077584:2-Methoxyestradiol; D020558:GTP Phosphohydrolases; C474315:SEPTIN9 protein, human; D058112:Septins; D017239:Paclitaxel