Characterisation of a multimeric protein complex associated with ERp57 within the nucleus in paclitaxel-sensitive and -resistant epithelial ovarian cancer cells: the involvement of specific conformational states of beta-actin.
Ovarian cancer is the second most frequently diagnosed malignancy of the reproductive system and is the leading cause of gynecological cancer mortality. Although the majority of advanced ovarian carcinomas initially respond successfully to taxane-based chemotherapy, resistance to chemotherapy remains the primary factor accounting for the low 5-year survival in this patient population. Recent data obtained by our group demonstrate that the disulphide isomerase ERp57 is strongly modulated in paclitaxel resistance suggesting that it may represent a chemoresistance biomarker in ovarian cancer. In the present study, we characterise a nuclear multimeric complex where ERp57 is associated with protein species involved in cell division and gene expression, as Nucleolin, Nucleophosmin, Vimentin, Aurora kinase C and beta-actin. In particular, we show that the occurrence of the interaction of nuclear ERp57 with beta-actin is associated with paclitaxel resistance and that specific actin conformations modulate this complex. We propose the involvement of the nuclear ERp57 complex in mechanisms associated with chromosome segregation in which specific conformational states of actin play a role in the pathway involved in paclitaxel resistance.
Cicchillitti
Lucia
L
Department of Oncology, Research Laboratories, Catholic University, I-86100 Campobasso, Italy. luciacic@yahoo.com
Della Corte
Anna
A
Di Michele
Michela
M
Donati
Maria Benedetta
MB
Rotilio
Domenico
D
Scambia
Giovanni
G
D000199:Actins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D020090:Chromosome Segregation / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D006801:Humans; D046912:Multiprotein Complexes / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology; D013329:Structure-Activity Relationship
D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; D046912:Multiprotein Complexes; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D017239:Paclitaxel