title: Alterations in nuclear pore architecture allow cancer cell entry into or exit from drug-resistant dormancy.
abstract: Phenotypic diversity arises in tumors just as it does in developing organisms, and tumor recurrence frequently manifests from the selective survival of divergent drug-resistant cells. Although the expanding tumor cell population may be successfully targeted, drug-resistant cells may persist and sustain the tumor or enter dormancy before igniting a future relapse. Herein, we show that partial knockdown of nucleoporin p62 (NUP62) by small-interfering RNA confers cisplatin resistance to cultured high-grade ovarian carcinoma cells. Treatment with NUP62 small-interfering RNA and cisplatin leaves resistant cells in a state of dormancy; some dormant cells can be induced to proliferate by transient induction of NUP62 expression from an ectopic expression construct. In addition to suggesting functional links between nuclear pore complex architecture and cancer cell survival, the culture system provides a novel experimental window into the dynamics of tumor cell drug resistance and dormancy.
authors.affiliation: Department of Pathology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Tamara
authors.initials: T
authors.lastname: Kalir
authors.forename: Jamal
authors.initials: J
authors.lastname: Rahaman
authors.forename: Peter
authors.initials: P
authors.lastname: Dottino
authors.forename: D Stave
authors.initials: DS
authors.lastname: Kohtz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D022022:Nuclear Pore / Q000187:drug effects* / Q000235:genetics; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D028861:Nuclear Pore Complex Proteins; D034741:RNA, Small Interfering; C049312:nuclear pore protein p62; D002945:Cisplatin
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