Inhibition of Anchorage-independent Growth of Transformed NIH3T3 Cells by Epithelial Protein Lost in Neoplasm (EPLIN) Requires Localization of EPLIN to Actin Cytoskeleton

Epithelial protein lost in neoplasm (EPLIN) is a cytoskeleton-associated protein characterized by the presence of a single centrally located lin-11, isl-1, and mec-3 (LIM) domain. We have reported previously that EPLIN is down-regulated in transformed cells. In this study, we have investigated whether ectopic expression of EPLIN affects transformation. In untransformed NIH3T3 cells, retroviral-mediated transduction of EPLIN did not alter the cell morphology or growth. NIH3T3 cells expressing EPLIN, however, failed to form colonies when transformed by the activated Cdc42 or the chimeric nuclear oncogene EWS/Fli-1. This suppression of anchorage-independent growth was not universal because EPLIN failed to inhibit the colony formation of Ras-transformed cells. Interestingly, the localization of EPLIN to the actin cytoskeleton was maintained in the EWS/Fli-1– or Cdc42-transformed cells, but not in Ras-transformed cells where it was distributed heterogeneously in the cytoplasm. Using truncated EPLIN constructs, we demonstrated that the NH(2)-terminal region of EPLIN is necessary for both the localization of EPLIN to the actin cytoskeleton and suppression of anchorage-independent growth of EWS/Fli-1–transformed cells. The LIM domain or the COOH-terminal region of EPLIN could be deleted without affecting its cytoskeletal localization or ability to suppress anchorage-dependent growth. Our study indicates EPLIN may function in growth control by associating with and regulating the actin cytoskeleton

The American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock: Executive Summary

10.1097/PCC.0000000000001259Pediatric Critical Care Medicine189884-89

American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock

10.1097/CCM.0000000000002425Critical Care Medicine4561061-1093CCMD