Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation

NHERF1/EBP50 (Na⁺/H⁺ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA.

Postoperative Epidural Analgesia using 0.1% Levobupivacaine or 0.1% Ropivacaine Combined with Sufentanil in Gynecologic Surgery / 대한마취과학회지

BACKGOUND: Ropivacaine and levobupivacaine are recently introduced amide local anesthetics that are structurally similar to bupivacaine. In this study, we compared the quality of postoperative analgesia and the side effects of 0.1% ropivacaine/sufentanil and 0.1% levobupivacaine/sufentanil. METHODS: Sixty patients scheduled for gynecologic surgery under general anesthesia were randomized to receive either 0.1% ropivacaine with sufentanil (ropivacaine group) or 0.1% levobupivacaine with sufentanil (levobupivacaine group) for postoperative epidural analgesia using a patient-controlled analgesia pump at a rate of 5 ml/h during the 48 hour period following surgery. Visual analogue scale (VAS) scores at rest and on coughing, sitting and movement, the degree of ambulation, additional analgesic requirements and side effects were assessed. RESULTS: In the levobupivacaine group, VAS scores at rest and on coughing, sitting and movement were lower than in the ropivacaine group (P < 0.05). In the ropivacaine group more patients were able to walk unaided (P < 0.05). There were no differences in local anesthetic consumption, additional analgesic requirements and side effects between the groups. CONCLUSIONS: Both 0.1% ropivacaine with sufentanil and 0.1% levobupivacaine with sufentanil provided effective postoperative epidural analgesia, but ropivacaine produced lesser motor block.