LIMK2 Mediates Resistance to Chemotherapeutic Drugs in Neuroblastoma Cells through Regulation of Drug-Induced Cell Cycle Arrest

• DOI: 10.1371/journal.pone.0072850
• Publication Date: 2013-08-21T21:03:33Z
• Authors: Cristina Gamell; Alice V. Schofield; Randy Suryadinata; Boris Sarcevic; Ora Bernard
• Keywords: 0301 basic medicine; Science; Q; Cell Cycle; R; 610; Lim Kinases; 600; Acetylation; Antineoplastic Agents; Nerve Tissue Proteins; Microtubules; Up-Regulation; 3. Good health; Neuroblastoma; 03 medical and health sciences; Drug Resistance, Neoplasm; Cell Line, Tumor; Medicine; Humans; Research Article; DNA Damage

Drug resistance is a major obstacle for the successful treatment of many malignancies, including neuroblastoma, most common extracranial solid tumor in childhood. Therefore, current attempts to improve survival neuroblastoma patients, as well those with other cancers, largely depend on strategies counter cancer cell drug resistance; hence, it critical understand molecular mechanisms that mediate chemotherapeutics. The levels LIM-kinase 2 (LIMK2) are increased cells selected their microtubule-targeted drugs, suggesting LIMK2 might be possible target overcome resistance. Here, we report depletion sensitizes SHEP several and this sensitivity correlates enhanced cycle arrest apoptosis. Furthermore, show modulates microtubule acetylation tubulin Polymerization Promoting Protein 1 (TPPP1), may participate mitotic block induced by drugs through regulation network. Moreover, LIMK2-depleted also an certain DNA-damage agents, act general pro-survival factor. Our results highlight exciting possibility combining specific inhibitors anticancer multi-drug resistant cancers.